of the A and B specificities were established before the discovery of the latter loci and, to avoid renumbering, the

existing numbers for the A and B loci were retained. Also note in Table 222 that many of the broad specificities are subdivided into two or more different specificities because of the detection of discrete gene products by monospecific antisera. Monospecific antisera by definition react only with antigenic determinants unique to the specific antigen. This process of splitting previously recognized antigens is still going on. Table 223 lists the broad specificities and their designated split specificities. Also listed are associated antigens (#), which are variants of the original broad specificity and not splits as previously defined. There are no 4 or 6 allelic assignments within the A and B loci, because these numbers were reserved for the leukocyte antigen systems under active investigation at the time the nomenclature was established. The antigens originally called 4 and 6 are now termed Bw4 and Bw6. Every HLA-B locus molecule and some HLA-A locus molecules carry either the Bw4 or the Bw6 antigenic determinant. The distribution of Bw4 and Bw6 determinants on HLA-A and HLA-B locus gene products is found in Table 224. Current nomenclature was recommended during the Tenth International Histocompatibility Workshop in 1987; minor modifications were made in 1990, and total implementation was achieved after the Eleventh International Workshop in 1991. Many HLA allelic variants were discovered by nucleotide and amino acid sequence data that are not detectable by traditional serologic techniques. This complexity necessitated the development of the following nomenclature for HLA genes: 1. HLA- designates the MHC. 2. A capital letter indicates a specific locus (A, B, C, D, etc.) or region. All genes in the D region are prefixed by the letter D and followed by a second capital letter indicating the subregion (DR, DQ, DP, DO, DN, etc.). 3. Loci coding for the specific class II alpha and beta peptide chains are identified next (A1, A2, B1, B2). 4. Specific alleles are designated by * followed by a twodigit numeral defining the unique allele. The following two, two-digit numeral defines the variant of the specific allele. For example, the serologically defined HLA-B27 specificity is actually made up of seven distinct allelic variations. These alleles are now defined as HLA-B *2701 through *2707. The nomenclature of certain alleles contains a fifth digit, such as HLA-Cw *02021 and *02022. The fifth digit indicates that the two variants differ by a silent nucleotide substitution but not in amino acid sequence. Some examples of current HLA genetic nomenclature are