The HLA Complex and the Pathogenesis of Infectious Diseases

The HLA complex is a multigene family on the short arm of human chromosome 6 that encodes molecules critical to self-nonself discrimination (figure 1). Cell surface molecules of two types are involved in this process. Those determined by HLA-A, HLA-B, and HLA-C genes, termed class I molecules, constitute a heavy chain of molecular weight -45,000 that is noncovalently associated with a 12,000 molecular weight light chain, (32 microglobulin. The HLA-A, HLA-B, and HLA-C loci constitute the genes for the class I heavy chains; (32 microglobulin is separately encoded on chromosome 15. Class I molecules are involved in targetcell recognition by a subset of T cells that usually display the surface molecule T8; such cells have been commonly associated with functions of suppressor and cytotoxic cells (including the killing of virus-infected target cells). The HLA-D region encodes a complex of gene products (class II molecules) that are also represented on cell surfaces as heterodimers (-34,000 and "-29,000 Mr). The structural genes for both chains of these molecules are located within the HLA-D region. Three distinct class II molecular species have been characterized; these are termed DR, DQ (formerly MB or DC), and DP (formerly SB). Class II HLA molecules on the surface of antigen-presenting cells are essential for recognition of antigen by T cells that usually express the T4 marker and that have been associated with initial recognitive events in a T cell response, particularly of cells with helper or inducer activities.