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INTRODUCTION

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.

FIGURE 62–1

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.

TABLE 62–1Comparison of Class I and Class II MHC Proteins

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 2019, there are at least 4,300 HLA-A alleles, 5,200 HLA-B alleles, 3,900 HLA-C alleles, and more than 5,000 HLA-D 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 produced).

The class I MHC ...

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