In transplantation, an organ or tissue from one person is “grafted” to another person. A major barrier to the success of these life-saving procedures is the immune system, which attacks any cells it sees as foreign. Graft survival is largely determined by the donor’s and recipient’s major histocompatibility complex (MHC) proteins, which present antigens to T cells. In humans, these proteins are encoded by the human leukocyte antigen (HLA) genes. (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.
TABLE 62–1Comparison of Class I and Class II MHC Proteins ||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 |
The human leukocyte antigen (HLA)–gene complex. A, B, and C are class I loci, and each gene encodes an alpha chain that pairs with the same β2-microglobulin. DP, DQ, and DR are class II loci, and each gene encodes alpha and beta chains that pair with each other.
Each person has two HLA haplotypes (i.e., two sets of these genes—one on the paternal and the other on the maternal chromosome 6). These genes are highly polymorphic (i.e., there are many alleles of the class I and class II genes). For example, as of 2020, there are at least 20,000 HLA Class I alleles and 7700 HLA Class II alleles, and more are being discovered. However, an individual inherits only a single allele at each locus from each parent. Expression of these genes is codominant (i.e., the proteins encoded by both the paternal and maternal genes are ...