nature OF ANTIGENS MAJOR & HIOSTOCOMPATIBILITY COMPLEX (MHC) |

Two signals that B cells require to produce antibodies Immunogens Antigens

1. Interaction of B cell with an antigen  Any agent capable of triggering an adaptive (acquired)  Not all antigens are immunogens
2. Interaction of B cell with activated T helper cell immune response by inducing the formation of - cannot produce antibodies
- Since B cell is an antigen presenting cell, T cell needs do be processed or degraded in
antibodies or sensitized T cells  Specifically reacts with a component of
order for it to get activated and bind with a B cell
o Antibodies: called immunoglobulins; used to identify the immune response (e.g., antibodies
- T helper cells produce cytokines that helps the B cell transform to plasma cell and
and neutralize pathogens or T cell receptors), but may not be
memory cell
- can be used in in vitro tests which can be used to able to evoke an immune response
3 Main Antigen Presenting Cell (APCs) identify the presence or absence of antigens in the  In discussing serological reactions or
1. Dendritic Cell – found in skin, muscles and other tissues blood and serum markers particular names of substances such
2. B Cell - (e.g., Needle stick injury with an Hep. B patient, with as blood groups, the term antigen is
3. Macrophage full dosage of Hep B vaccine, the body is already still more commonly used
primed with the virus. The antibody binds with the
Vaccines are immunogenic because they will elicit an immune response. virus so that it doesn’t attack the liver. Since they
- during COVID-19 vaccination, the vaccine contains a small amount of the attenuated are viruses, they need a host cell. When the
virus by a chemical antibody binds to the virus, it won’t get in the host
- the antigen is now recognized by the body as non-self, then the immune response will cell = they won’t replicate = deads)
do its work o Sensitized T cells: T cells that are exposed to an
antigen and activated
 Macromolecules (at least 10,000 Da)
 All immunogens are antigens

Innate Immune Response Factors Influencing the Immune Response

 also called Natural Immunity 1. Age – older individuals have a decreased response to antigenic stimulation and are less able to
 Nonspecific response to pathogens distinguish between self and non-self-antigens; newborns and infants do not have a
- nonspecific can target many antigen completely developed immune system
 No prior exposure is required; response lacks memory and specificity - newborns and infants – have poorly developed immune system
 Key cells: Antigen-Presenting Cells (APCs), Granulocytes, Mast Cells - older individuals – declining immune system
- granulocytes – white blood cells that contain granules
 Mast Cell – named as Basophil when it goes to tissue 2. Overall health – malnourished, fatigued, or stressed individuals have a decreased immune
 Macrophage – named as Monocyte when it goes to tissue response.
- different tissues have different macrophage; if it goes to other parts of the body - when a person is malnourished, there are not enough proteins to produce antibodies.
Specifically, Amino acids from food diet which are the building blocks to produce proteins
example of Innate Immune Response is the Passive Immunity of a mother to baby. Since babies under
6 months old cannot produce their own antibodies, they’re protected by the antibodies of the mother 3. Dose – a significant quantity of an immunogen must be present for an adaptive immune
through breast feeding (IgA) response to take place. The larger the amount of the immunogen, the greater the immune
response
- if the infecting dose of a virus is high, there are more immune response because the body will
try to attack all the pathogens to eliminate them from the body
Adaptive Immune Response
 Acquired immunity 4. Route of inoculation - determines the actual amount of immunogen needed to generate an
 Specific recognition of individual pathogens immune response and also determines which cell populations will be involved in the response
- specific can target one antigen - E.g., Intramuscular Vaccination, there are adverse reaction when a certain vaccine is taken
 Ability to remember a prior exposure; response is increased on repeated exposure to the same orally or by other route
pathogen
 Key cells: lymphotcytes (T cells and B cells) 5. Genetic capacity – a genetic predisposition may be involved that allows individuals to respond
to particular immunogens

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- Combined immunodeficiency (CID) – prone to bacterial infections
- Hypogammaglobulenemia – disorder caused by low serum immunoglobulin or antibody levels
Traits or Factors of Immunogens
 Macromolecular Size
An antigen must have a high molecular weight to be immunogenic
In order for an agent to become immunogenic, they should be macromolecules. But not all
biomolecules are immunogenic. The most effective immunogens are proteins, polysaccharides,
nucleic acids+carbohydrate, lipids+carbohydrates and glycoproteins
 Usually, an immunogen must have a molecular weight of at least 10,000 Daltons or 10kg Da to
be recognized by the immune system and the most active immunogens typically have a
molecular weight of over 100,000 Daltons
 However, there are exceptions because a few substances with a molecular weight of lower than
1,000 have been known to induce an immune response (e.g., hapten-protein complexes)
- such as haptens with low molecular weight. When haptens is complexed to proteins or with
higher molecular weight biomolecules, they will then be immunogenic and cause immune
response
 For the most part, the rule of thumb is that the greater the molecular weight, the more potent
the molecule is as an immunogen
 Foreigness
An antigen must be recognized as non-self to be immunogenic
 Our immune system is able to distinguish between self and non-self
 Those substances recognized as non-self are immunogenic
 Taxonomically distant substances are also recognized as non-self and are immunogenic
 Note also that it is possible for self-antigens to be immunogenic
 Loss of tolerance (non-responsiveness) to self-antigens is called autoimmunity
- attacks own cells, antigens, or even healthy tissues = organ damage, multiple organ failure
- E.g., SLE – basement membrane of the lungs and kidney gets damaged
 A specific antibody directed against your own antigens is called an autoantibody
- E.g., Antinuclear antigen in Systemic Lupus Erythematosus (SLE)
 Immunologic disorders caused by the production of autoantibodies, and subsequent damage to
affected organs(s) is called an autoimmune disorder
nature OF ANTIGENS MAJOR & HIOSTOCOMPATIBILITY COMPLEX (MHC) |
 Chemical Composition and Complexity
Immunogenicity is also determined by a substance’s chemical composition and molecular
complexity
 Proteins and polysaccharides are the most effective immunogens – larger molecular weight
 Synthetic polymers such as Teflon and nylon (used in making artificial heart valves, prosthetics,
and other medical appliances) are non-immunogenic
 Carbohydrates are less immunogenic than proteins
o Carbohydrates complexed with proteins and lipids (glycoproteins (Rh and Lewis antigens)
and glycolipids (A, B, H antigens), respectively)
o Capsular polysaccharide of certain bacteria and fungi (e.g., S. pneumonia, H. influenza
serotype B, and Cryptococcus neoformans) is an important immunogen
 Lipids and Nucleic Acids, by themselves or in their pure form, are not immunogenic
o They must be complexed with carrier molecules (e.g., proteins) to become immunogenic
o DNA Complex with proteins (e.g., DNA-Protein Complex in SLE)
 Antinuclear Antigens – antibodies found in the serum of px with SLE; antinuclear because
the DNA is attacked = autoimmune disorder
- the more complex, more immunogenic
 Degradability
An antigen must be subject to antigen processing (enzymatic digestion) to be immunogenic
- it has to undergo enzymatic digestion especially for Class II MHC Molecule since it interacts
with process polypeptides to present it to the APCs
 It has to be degraded, because if not, it cannot be presented to antigen-presenting cells and
cannot attract the T cell
- poor immunogen; no cytokines will be produced and B cells cannot mature
 Antigen processing involves enzymatic digestion to create small peptides or pieces that can be
complexed to MHC molecules to present to responsive lymphocytes
 A macromolecule that cannot be degraded and complexed to MHC molecules would be a poor
immunogen
 Most protein antigens need to be processed and presented by antigen-presenting cells. The
digested fragments become bonded to MHC molecules on the surface of the APC and this
whole complex then binds to T-cells. artificial heart valves, prosthetics, and other medical
appliances) are non-immunogenic
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 nature OF ANTIGENS MAJOR & HIOSTOCOMPATIBILITY COMPLEX (MHC) |
Other requirements for Immunogens:
 Genetics
 Low-molecular-weight molecule; by itself, is not immunogenic
o The number and quality of the genes for the MHC proteins vary in a population of animals
 has to bind with a bigger biomolecule to be immunogenic proteins like:
and this will affect the ability of the individual animal to develop an immune response.
 Proteins
o Individual animals can also vary with regard to their collection of T and B cell antigen
 Complex Carbohydrates
Receptors
 Polysaccharides

 Dose and Route of Administration of the antigen:

o Too low or too high a dose of antigen can actually induce a state of tolerance or non-
Characteristics:
responsiveness in the animal.
 Haptens are too small to be recognized by the immune system
o The route of immunization can cause very different responses; for instance, antigens that
 When combined with carrier molecules, they become immunogenic
come in contact with mucous membranes generally induce IgA antibodies, whereas
 Haptens bind to the B cell receptor (with or without carrier molecules)
intramuscular and intravenous immunization often induces IgG and IgM responses
 Has only one antigenic determinant or epitope (can’t cross-link with more than one antibody)
- route of inoculation is depending on which cells are the targets
- Example:
 Intramascular (Deltoid and Vastus lateralis)
– dendritic cells and other immune cells present in the muscles
– Vaccines especially with adjuvants are inoculated here to increase the
effectiveness of the vaccine
– There are salts in adjuvants which may cause adverse effects to the
skin and mucous membrane that’s why it has to be in the muscle and so
that there will be more time for the vaccine to be exposed to the
immune cells
and in order to stabilize the integrity of the immunogens
 Oral vaccine – mucosa-associated lymphoid tissue (MALT)
 Joints, Cervical Region – lymph nodes

Fab portion attaches to the epitope each Fab attaches to 1 antigen

(Antigen-Binding
Fragment)
Fc portion attaches to other surfaces and cells
(Crystallizable
Fragment)
 part of Fab; the top portion; will recognize to only one target
 It has to be one target because it will cause a cross-reaction;
 there is a specific shape like the lock-and-key in enzymes;
Paratope  locks perfectly to the epitope. Hence, it has specificity

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 also called antigenic determinant site; it is the key molecular portion of the
- agent that would be recognized by the antibody by its paratope
 immunogen that is recognized by the cells of the immune cells, specifically the T or B cells
 Linear Epitope
 also called sequential epitopes
 consist of sequential amino acids on a single polypeptide chain
 There may be several different types on one chain.
 Conformational Epitope
 result from the folding of a polypeptide chain or chains, and nonsequential
amino acids are brought into close proximity
- there are bonds attached that’s why it’s
How an Epitope relates to an Immunogen:
The first signal is when B lymphocyte recognized the antigen or pathogen. There is no prior
degradation. B-cell activation is dependent on the signals.
The surface immunoglobulins or surface antibodies that binds on the surface B-cell will act as B-cell
Receptor (BCR). They will attach to the immunogen then gets activated.
After that, the second signal occurs which is when the APCs engulf the immunogen then digestesd.
Antigen-Presenting Cell should be able to process the immunogen into smaller peptides to present it to
CD4 T-helper cell.
If it’s not processed, they won’t function as an immunogen. After processing it to a smaller peptide it
will undergo degradation or it will be fragmented in order for it to be presented to the T helper cells
via MHC II molecules then the B cell will get activated and form memory and plasma cells.
CD4 will act as a correceptor to activate the T helper cell. Activated T helper cell will now
produce cytokines that will activate the other T helper cells to attract to the site of injury or to the
area where there are high amounts of cytokines.
When infected with HIV, CD4 and T helper cell will decrease hence, no one is left to help activate B cell
produce antibodies. However, there are still some HIV antibodies formed but CD4 is still low.
nature OF ANTIGENS MAJOR & HIOSTOCOMPATIBILITY COMPLEX (MHC) |
B Lymphocytes
 Linear and conformational epitopes on the immunogen’s surface are recognized by the surface
antibodies, which act as the B cell receptors.
 If the immunogen is able to crosslink the B cell surface antibodies, then it could trigger B cell
activation.
 Prior degradation of the immunogen is not necessary
T Lymphocytes
 For T cells to be able to recognize an immunogen, it must first be degraded into small peptides
by an antigen-presenting cell (APC).
 Processed peptides then form a complex with MHC proteins and are carried to the surface of
the APC.
 “Presented” peptides are then recognized by the T cells through their receptors (T cell receptor
and CD4 or CD8 co-receptor molecules)
 is a substance administered with an immunogen (i.e., vaccine) that increases or strengthens the
immune response to provide immunity to a particular disease (i.e., helps to make the
immunization more effective) Examples: aluminum salts, AS04, MF59, etc.
 Adjuvants work by targeting the antigen-presenting cells (APCs), which are key to the adaptive
immune response
o Adjuvants protect immunogens from degradation and allow a longer response time that
attracts a large number of immune system cells to the injection site
o Adjuvants in vaccines make antigens more potent; hence, less dose of the antigen is required
 Adjuvanted vaccines can cause more local reactions (such as redness, swelling, and pain at the
injection site) and more systemic reactions (such as fever, chills, and body aches) than non-
adjuvanted vaccines
- vaccines with adjuvants should not be administered orally and subcutaneously.
Antigens can be placed in broad categories according to their
relationship to the host:
 Autoantigens – are those antigens that belong to the host
- E.g., HLA, MHC – Endogenous
 Alloantigens – are from other members of the host’s
species and are capable of eliciting an immune
response
- E.g., Donor has an antigen while the recipient doesn’t.
The recipient’s immune response will react since the donor’s antigen is missing in the
recipient’s blood. The body will form alloantibodies.
- Those that are in the donor’s blood are called alloantigens
- This process is now called Alloimmunization. You are immunized by the antigen of another
person
- Incompatibility transfusion will cause an immune response. The antibodies will bind to
RBCs then they are now tagged for destruction = Immune-Mediated Red Blood Cell
Destruction
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- They will be recognized as damaged RBCs or abnormal RBCs in the Spleen since they were
tagged for destruction
- In vivo sensitization – the binding of an antibody to its target antigen
 Detected by: Coombs’ Test / Antihumanglobulin Test. Specifically, DAT
 Heteroantigens – are from other species, such as other animals, plants, or microorganisms
- post-streptococcal nepherulonephritis
 Heterophile Antigens – are heteroantigens that exist in unrelated species, but are either
identical or closely related in structure so that antibodies to one will cross-react with the
antigen of the other  molecular mimicry
 Type 1 Diabetes Mellitus
 Also called juvenile (relating to young people) or insulin-dependent diabetes mellitus.
 It is an organ-specific autoimmune disease caused by the autoimmune response against
pancreatic -cells.
- decreased -cells results to the decrease of insulin since -cells are the ones who produce it
- hypoglycemic cell  no fuel or glucose to make ATP
- insulin resistant – insulin won’t react to the cell. Glucose can’t get in;
- insulin deficiency – the insulin will react with the cell but deficient
 Lymphocytic infiltration and destruction of insulin-producing pancreatic ß-cells.
- when transfusing incompatible blood = transfusion reactions
A group O Rh-negative patient cannot receive or transfuse with a blood from a group O Rh-positive
donor. Their serum will be incompatible since the recipient doesn’t have a D antigen. The body will
recognize the group O Rh-positive blood as foreign (qualifies the factors; Foreigness and Complexity)
since it is a combination of different biomolecules like lipids and carbohydrates so it qualifies as an
immunogen.
Since the body has recognized the Group O Rh-positive blood as an immunogen, the body will produce
immune response and will produce Alloantibodies / Alloanti-D.
nature OF ANTIGENS MAJOR & HIOSTOCOMPATIBILITY COMPLEX (MHC) |
During the second exposure, since the body has been primed with the D antigen, the antibodies will
bind with the RBC then goes to the spleen where it gets destroyed. The transfused blood will have a
decreased chance of survival which results to the patient of having Anemia.
O- can only give pumped RBC to A+ during emergencies. It must not be whole blood because the
plasma of O- has naturally occurring anti-A and anti-B that can attack the RBC.
 Rh Hemolytic Disease of the Newborn (HDN)
 happens when an Rh-negative mother has a baby with an Rh-positive father
- During the first pregnancy, when the baby inherits the Rh-positive from the father, the
mother becomes alloimmunized. During the second pregnancy, the mother already has
alloantibodies against the baby’s D antigen.
- the baby gets attacked inside the mother because the antibodies against the Rh antigens are
IgG. IgG antibodies can cross the placenta then goes to the blood stream of the baby that
causes Hydrops fetalis, edema or stillborn = HDFN
 Rheumatic Fever
 Antibodies against group A streptococcal cell walls can also react with (and thus damage)
human heart tissues
- antibodies directed against the antigens of the bacteria will try to cross-react to the
antigens of our heart muscle = heart disease and tissue damage
- molecules of the heart muscle are similar to the bacteria = molecular mimicry
- inflammatory will happen or immune complex formation
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 nature OF ANTIGENS MAJOR & HIOSTOCOMPATIBILITY COMPLEX (MHC) |
 Infectious Mononucleosis (Kissing Disease)  By identifying the genes that determine HLA type, Dausset created the possibility of matching
organ donors and recipients, thereby dramatically decreasing the risk of rejection following
 Infectious mononucleosis is caused by the transplantation
Epstein-Barr virus (EBV, human herpesvirus
type 4) and is characterized by fatigue, Genetics of the Major Histocompatibility Complex
fever, pharyngitis, and lymphadenopathy
 Heterophile antibodies are not directed against
Epstein-Barr Virus (EBV) or EBV-infected
cells
- Heterophile antibodies because it will
cross-react with sheep, horse or cattle
RBCs or antigen
- it is a human antibody but it will also
react with the antigen or RBCs of other
species

 The heterophile antibody is present in 40-60% of patients with infectious mononucleosis
 antibody titers are highest during the first 4 weeks of disease
- the person gets infected through direct contact with a contaminated person from his/her
secretions especially to those with multiple sex partners
 Genes coding for the MHC molecules in humans are found on the short arm of chromosome 6
and are divided into three categories or classes
- if there is a genetic defect of this, MHC proteins can no longer be produced
 At each of these loci (physical location of a gene), there is
the possibility of multiple alleles. Alleles are alternate
forms of a gene that code for slightly different varieties
of the same product.
o HLA-A: ~ 3,356 alleles
o HLA-B: ~ 4,179 alleles
o HLA-C: ~ 2,902 alleles

Organ Transplantation
Before organ transplantation we need to consider HLA Antigen or MHC expressed on WBCs. Blood
typing needs to be done which should match including the HLA Antigens.
 The probability that any two individuals will express the same MHC molecules is very low.
Identical twins have the same genetic make up but if organs are received from other people, the
 There is a possibility of two different alleles for each gene on the chromosome unless that
success of the organ transplant is less. So dapat same jud ang HLA.
person is homozygous (has the same alleles) at a given location
 MHC molecules of both individuals are incompatible = treated as foreign = tissue is
 Formerly called human leukocyte antigens (HLA)
rejected
 French scientist Jean Dausset was awarded the 1980 Nobel Prize for Physiology or Medicine.
 Both individuals express the same MHC molecules = tissue is accepted
 He was recognized for his identification of human leukocyte antigens and the genes that code
for them. He called the set of genes the human leukocyte antigen (HLA) group.

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 nature OF ANTIGENS MAJOR & HIOSTOCOMPATIBILITY COMPLEX (MHC) |
Structure of MHC I Molecule
 Glycoprotein dimer of noncovalently bonded polypeptide chains
o Heavy chain: α-chain (44 kDa); folded into 3 domains: α1, α2, and α3; anchored into the
Haplotype cell membrane via a hydrophobic transmembrane segment; CD8 coreceptor (of
cytotoxic T cell) binds to the α3 domain; coded by separate genes in chromosome 6
o Light chain: ß2-microglobulin (12 kDa); does not penetrate into the cell membrane;
essential for the proper folding of the α-chain; coded by a separate gene in
Haplotype chromosome 15
murag package

- 2-microglobulin  function is to fold

the structure
 MHC Genes are described as codominant, meaning two alleles are expressed to an equal - Peptide-binding cleft  processed
degree within an organism; neither allele is recessive, and the phenotypes of both alleles are peptide attach
expressed in the heterozygote
 MHC Genes are closely linked; thus they are inherited together as a package called a haplotype  The α1 and α2 domains form a CLOSED
groove (called the peptide-binding cleft)
- Haplotype from the mother and haplotype from the father will fuse during fertilization at the top of the molecule that functions
(inig juggybells). Meaning, both are codominant or inherited by the baby as the peptide-binding site in antigen
- the most important role of MHC is for antigen presentation. Without it, antigen won’t recognition
function as immunogen therefore the genes that coat for MHC coating should be normal
- there should be adequate number of MHC molecules in our WBCs so that the processed Examples of MHC I Molecules:
peptides will be successfully presented to the surface so that the T helper cell or CD4+ HLA-A, -B, -C
will recognize the processed peptides and produce cytokines resulting for the B cells to
produce antibodies.
Each colored circle represents an allele (different version of the same gene) of a heterozygous
person. Role of the Class I MHC Molecule

 Class I molecules mainly present peptides synthesized within the cell to CD8+ (cytotoxic) T
cells
 Class I molecules are thus the “watchdogs” of viral, tumor, virus-infected cells and certain
parasitic antigens that are synthesized within the cell
- their main role is in antigen presentation
- both MHC I and MHC II are integral proteins
- their proteins traverse with the lipid bilayer

 Class I MHC
 Type of antigen processed: Endogenous
 Class I MHC molecules are expressed on all nucleated cells but differ in their level of
expression.
o High expression: lymphocytes and myeloid cells
o Low expression: hepatocytes, neural cells, muscle cells, and sperm cells

- expression  what is expressed in their cell membrane

Does mature RBCs contain MHC I?

No because they are not nucleated or their nucleus is devoid na or nawala na in the spleen

 Recognized by the cytotoxic (CD8+) T lymphocytes

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 nature OF ANTIGENS MAJOR & HIOSTOCOMPATIBILITY COMPLEX (MHC) |
Class I MHC-Peptide Interaction Structure of MHC II Molecule
Class I molecules are synthesized in the Rough Endoplasmic Reticulum  Glycoprotein heterodimer (2 different chains) of noncovalently bonded polypeptide chains
o Alpha-chain: 34 kDa
1. Enzymatic digestion of endogenous antigens o Beta-chain: 29 kDa
(proteins) is carried out by the proteasome  Both the alpha- and beta-chains are anchored to the cell membrane
2. Once degraded, the peptides are pumped into  CD4 coreceptor (of helper T cell) binds to the ß2 domain
the lumen of the rough endoplasmic  The α1 and ß1 domains form the peptide-binding cleft at the top of the molecule that
reticulum by ATP-dependent transporter functions as the peptide-binding site in antigen recognition
proteins (TAP1 and TAP2) o The groove or cleft is OPEN – it allows the class II molecule to capture longer peptides than
- TAP  Transporter-Associated with class 1 molecules

Antigen Processing
3. Alpha-chain of the class I MHC molecule
associates with the 2–microglobulin domain
4. The peptide attaches to the peptide-binding
cleft of the alpha-chain of the class I MHC
molecule
5. The peptide–class I MHC complex is
transported to the Golgi complex and then to
the cell surface.
- they fuse to the membrane because the golgi
complex is made up of acinular
molecules of our plasma membrane since it is a lipid
bilayer
6. The cytotoxic (CD8+) T lymphocyte recognizes the antigen and
produces cytokines (e.g., perforin and granzyme) that result in Role of Class II MHC Molecule
the lysis of the affected cell

 Class II MHC
 Type of antigen processed: Exogenous
 Class II MHC molecules are primarily expressed on antigen-presenting cells (APCs); also
expressed in the thymic epithelium.
 Recognized by the helper (CD4+) T lymphocytes
- E.g., bacteria is too large to be recognized, that’s why it has to be digested inside a  Class II molecules mainly present exogenous antigen to CD4+ (helper) T cells.
phagocyte. It is processed into small peptides then recognized by CD4 which is a o Exogenous proteins presented by class II molecules are those taken into the cell from the
correceptor outside and degraded.
 Class II molecules help to mount an immune response (humoral) to bacterial infections or other
o Expression / Expressed: products of genes are converted into molecules or structures pathogens found outside cells.
that are present and operating in the cell.
o Recognized: the presence of peptides (antigens) is acknowledged or “seen” by the T cells
when combined with MHC molecules.

 Major class II molecules: HLA-DP, DQ, and DR

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 nature OF ANTIGENS MAJOR & HIOSTOCOMPATIBILITY COMPLEX (MHC) |
Class II MHC-Peptide Interaction

1. Newly synthesized class II MHC binds invariant chain to block the binding of endogenous
antigen.
2. MHC complex goes through the Golgi complex.
3. Invariant chain is degraded, leaving Class II Invariant Chain
Peptide (CLIP) fragment.
- Invariant chain contains a small peptide called CLIP
- It becomes a fragment when the invariant chain is destroyed
when it leaves the CLIP
- it does not bind to Class I because it cause autoimmunity
- CLIP – prevents autoimmunity para dili sila masayop ug bind
4. Exogenous antigen taken in, degraded and routed to the intracellular vesicle. (TAP is not
required here)
5. The CLIP fragment is exchanged for antigenic peptides.
6. Class II MHC antigenic peptide is transported to the cell surface.
7. Class II MHC peptide complex binds to CD4+ T cell
- once it binds, it activates in the 2 portion

CD28 recognizes and binds with B7 from the T helper cell. Once there is an interaction between the
receptors, the T cell gets activated. Once it is already an activated T cell, it will present to B cell.

Disease Symptoms HLA Strength of

Allele Association
Ankylosing Spongylitis Inflammation of the vertebrae of the spine B27 +++
Celiac Disease Diarrhea, weight loss, intolerance to gluten DQ2 +++
DQ8 +
Rheumatoid Arthritis Inflammation of multiple joints DR4 +
Type 1 Diabetes Increase in blood glucose because of DQ8 ++
destruction of insulin-producing cells DQ2 +

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