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INTRODUCTION

The human leukocyte antigen (HLA) system is synonymous withthe human major histocompatibility complex (MHC). These termsdescribe a group of genes on chromosome six that encode avariety of cell surface markers, antigen-presenting molecules, andother proteins involved in immune function.

The earliest HLA associations with rheumatic diseases, such asthe association of the HLA-B*27 allele at the HLA-B gene withankylosing spondylitis risk and the association of the HLA-DRB1*04 allele at the HLA-DRB1 gene with rheumatoid arthritis,were discovered several decades ago. As the study of HLAgenetics has evolved and expanded, the nomenclature has beencontinually altered, posing challenges for those attempting tofollow the science. However, knowledge concerning this geneticregion has evolved sufficiently, so the overall nomenclatureshould be more stable in the future, even though new alleles willbe identified and catalogued.

The genetics, nomenclature, and typing of HLA, as well as therelationships between HLA and rheumatic disease, are discussedhere. The older nomenclature that may still be encountered in theliterature is defined. The specific function of the MHC system,including the mechanisms of antigen presentation, is discussedseparately. (See"Major histocompatibility complex (MHC)structure and function".)

GENETIC STRUCTURE OF THE HLA REGION

The major histocompatibility complex (MHC) refers to a geneticregion containing hundreds of genes, including the HLA (human

leukocyte antigen) genes. Thus, the MHC is often also referred toas the HLA region. These HLA genes express their gene productson the surface of white blood cells and were originally recognizedto contain the genes encoding tissue antigens or tissue types.The function of these genes was revealed in rodent studies, in

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which they were identified as the factors responsible for rejectionof tissue grafts between unmatched individuals.

The MHC region lies on the short arm of chromosome six atposition 6p21.3. The classical MHC spans 3.6 megabases (Mb)and includes more than 200 genes, many of which are not knownto be involved in immune function. The localization of genesrelevant to the MHC outside the classical boundaries of thisregion and confirmation of extended linkage disequilibrium havesince led to the proposal for an extended MHC (xMHC). Thisregion spans 7.6 Mb and contains over 400 loci. The completestructure and gene map of the HLA region have been published[1,2].

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