The Role of the MHC Antigens in the Mature and Immature Host
1 Division of Pediatric Hematology, Oncology and Immunology, Amie Karen Cancer Center, Departments of Pediatrics, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, California, and Institut für Pathologie der Tierarztlichen Hochschule, Hannover, West Germany
During the past ten years, we have witnessed an explosion of knowledge regarding the histocompatibility antigens of man. Following the realization that the inheritance of this information was localized to one major histocompatibility complex (MHC) in each species, bone marrow transplantation was reassessed as a treatment for primary immunodeficiencies, aplastic anemia, and leukemia.1-3 Not long thereafter, disease associations with particular HLA alleles and phenotypes began to be appreciated.4,5 More recently, studies of 5everal complement deficiencies have linked the genes coding for such components to this same genetic complex, in man and in rhesus monkey, guinea pig, mouse, and chicken.6,7
The MHC of man is located on the short arm of chromosome 6. At this writing, it includes approximately ten boci with several others mapping nearby (Fig 1). The alleles at four loci are identified on lymphocytes by classical complement-dependent cytotoxicity: HLA-A, -B, -C, and -DR. HLA-D typing involves leukocyte interactions. (The relationship between the HLA-D and HLA-D related (HLA-DR) loci is presently unclear.) Three complement components (C2, C4, and Bf) and 21-hydroxylase deficiency have been mapped to the human MHC by linking serum deficiencies with particular MHC haplotypes. Allotypes for GLO-1 (glyoxylase) and PGM-3 (phosphoglucomutase) are defined by electrophoretic patterns.
The associations of MHC antigens with diseases such as ankylosing spondylitis, multiple sclerosis, cebiac disease, dermatitis herpetiformis, diabetes mellitus, rheumatoid arthritis, and psoriasis have renewed interest in the pathogenetic mechanisms of these diseases and raised the question of what primary functions these genes serve. For the complement loci, we know that the products translate into complement components. It is provocative that each of these complement components are directly involved in the activation or production of C3, a pivotal component in both the alternate and classical pathways.




