Two genetic loci control the murine immune response to A-gliadin, a wheat protein that activates coeliac sprue.

Abstract

Coeliac sprue is a disease in humans that is characterized by small intestinal mucosal injury and malabsorption. Ingestion of dietary gluten by susceptible individuals results in damage to the small intestine. The gliadin fractions of wheat gluten and similar proteins in rye and barley are known to activate the disease process1. The major histocompatibility complex (MHC) alleles HLA-B8, Dw3 and DRw3 occur at a high frequency in coeliac sprue2–5, suggesting that immunoregulatory mechanisms may be important in the pathogenesis of the disease. We recently reported that murine antibody responses to A-gliadin, a well characterized protein known to activate coeliac sprue1,6–9, are regulated by genes that map to H–2, the murine MHC10. However, it appeared that an additional genetic locus also might be important in regulating the immune response to gliadin proteins. We show here that two separate genetic regions determine the murine antibody response to A-gliadin: H–2 on chromosome 17 and the immunoglobulin heavy chain (CH) allotype locus (Igh) on chromosome 12. Possible ways in which these two loci could determine the response against A-gliadin are discussed.