3107

HLA-C

D6S204|HLA-JY3|HLC-C|PSORS1;major histocompatibility complex, class I, C;HLA-C;major histocompatibility complex, class I, C

HLA class I histocompatibility antigen, C alpha chain|HLA class I histocompatibility antigen, Cw-1 alpha chain|MHC class I antigen heavy chain HLA-C|human leukocyte antigen-C alpha chain|major histocompatibility antigen HLA-C

6p21.3

protein-coding

The extended human major histocompatibility complex (MHC) is a gene-rich region of about 7.6 Mb on chromosome 6, and includes a high proportion of genes involved in the immune response. Among these are the two Human Leukocyte Antigen (HLA) gene clusters, class I and class II, which encode highly polymorphic classical HLA-A, B, C and HLA-DR, DQ and DP genes, respectively. The protein products of the classical HLA genes are heterodimeric cell surface molecules that bind shortpeptides derived from non-self and self proteins, including infections and auto-antigens. The presentation of these HLA-anchored peptides to T lymphocytes triggers a cascade of responses in immune-associated genes that leads to adaptive immunity. Associations between HLA class II alleles and childhood leukemia have been reported in a number of studies. This could be due to the role of HLA allele-restricted peptide binding and T cell activation, or linkage disequilibrium to an MHC-linked "leukemia gene" in the pathogenesis of childhoodleukemia. Efforts are currently in progress to resolve these questions, using large leukemia case-control sample series such as the UK childhood cancer Study (UKCCS) and the Northern California childhood Leukemia Study (NCCLS). Here we review the background to these studies, and present a novel hypothesis based on the paradigm of HLA-associated auto-immune disease that might explain an infection-based etiology of childhood leukemia.