The success of tissue and organ transplants depends on the donor’s and recipient’s human leukocyte antigens (HLA) encoded by the HLA genes. These proteins are alloantigens (i.e., they differ among members of the same species). If the HLA proteins on the donor’s cells differ from those on the recipient’s cells, then an immune response occurs in the recipient. The genes for the HLA proteins are clustered in the major histocompatibility complex (MHC), located on the short arm of chromosome 6. Three of these genes (HLA-A, HLA-B, and HLA-C) code for the class I MHC proteins. Several HLA-D loci determine the class II MHC proteins (i.e., DP, DQ, and DR) (Figure 62–1). The features of class I and class II MHC proteins are compared in Table 62–1.
The human leukocyte antigen (HLA)–gene complex. A, B, and C are class I loci. DP, DQ, and DR are class II loci. C2 and C4 are complement loci. LT, lymphotoxin; TNF, tumor necrosis factor. PGM3, GLO, and Pg5 are adjacent, unrelated genes. (Reproduced with permission from Stites DP, Terr A, Parslow T, eds. Basic & Clinical Immunology. 9th ed. Originally published by Appleton & Lange. Copyright 1997 McGraw-Hill.)
Table 62–1Comparison of Class I and Class II MHC Proteins |Favorite Table|Download (.pdf) Table 62–1 Comparison of Class I and Class II MHC Proteins
|Feature ||Class I MHC Proteins ||Class II MHC Proteins |
|Present antigen to CD4-positive cells ||No ||Yes |
|Present antigen to CD8-positive cells ||Yes ||No |
|Found on surface of all nucleated cells ||Yes ||No |
|Found on surface of “professional” antigen–presenting cells, such as dendritic cells, macrophages, and B cells ||Yes1 ||Yes |
|Encoded by genes in the HLA locus ||Yes ||Yes |
|Expression of genes is codominant ||Yes ||Yes |
|Multiple alleles at each gene locus ||Yes ||Yes |
|Composed of two peptides encoded in the HLA locus ||No ||Yes |
|Composed of one peptide encoded in the HLA locus and a β2-microglobulin ||Yes ||No |
Each person has two haplotypes (i.e., two sets of these genes: one on the paternal and the other on the maternal chromosome 6). These genes are very diverse (polymorphic) (i.e., there are many alleles of the class I and class II genes). For example, there are at least 47 HLA-A genes, 88 HLA-B genes, 29 HLA-C genes, and more than 300 HLA-D genes, but any individual inherits only a single allele at each locus from each parent and thus can make no more than two class I and II proteins at each ...