The success of tissue and organ transplants depends on the donor’s and recipient’s major histocompatibility complex (MHC) proteins, which present antigens to T cells. The MHC proteins are alloantigens (i.e., they differ among members of the same species). In humans, these proteins are encoded by the human leukocyte antigen (HLA) genes, clustered on chromosome 6. (Note that we will use MHC and HLA interchangeably.) 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. 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 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, as of 2017, there are at least 3900 HLA-A alleles, 4800 HLA-B alleles, 3500 HLA-C alleles, and more than 4600 HLA-D alleles, and more are being discovered. However, an individual inherits only a single allele at each locus from each parent ...