title: Allelic T-cell receptor alpha complexes have little or no influence on susceptibility to type 1 diabetes.
abstract: We performed a multiple-affected-sib study to determine if T-cell receptor alpha-chain alleles affect susceptibility to insulin-dependent diabetes mellitus. Restriction fragment length polymorphisms were used to follow the segregation of allelic T-cell receptor alpha complexes within the families. The segregation of T-cell receptor alpha alleles in 29 multiplex families revealed no significant tendency for affected sibs to share T-cell receptor alpha-chain alleles more often than would be expected by chance alone (p greater than 0.2). In contrast, the same type of analysis for HLA alleles easily detected the well-known linkage of insulin-dependent diabetes mellitus susceptibility to the HLA complex (p = 0.003). We suggest that the importance of HLA alleles in insulin-dependent diabetes mellitus susceptibility and the lack of importance of T-cell receptor alpha alleles result from the different strategies by which HLA and T-cell receptor molecules achieve antigen-binding diversity: multiple loci and allelic diversity in the case of HLA; combinatorial, junctional, and N-region diversity in the case of the T-cell receptor. In this paper we also describe three new restriction fragment length polymorphisms of the T-cell receptor alpha complex and a new method for testing the significance of linkage in multiple-affected-sib studies.
authors.affiliation: American Red Cross Blood Services, Madison, WI 53705.
authors.forename: M J
authors.initials: MJ
authors.lastname: Sheehy
authors.forename: L M
authors.initials: LM
authors.lastname: Meske
authors.forename: C A
authors.initials: CA
authors.lastname: Emler
authors.forename: J R
authors.initials: JR
authors.lastname: Rowe
authors.forename: M H
authors.initials: MH
authors.lastname: Neme de Gimenez
authors.forename: C A
authors.initials: CA
authors.lastname: Ingle
authors.forename: A
authors.initials: A
authors.lastname: Chan
authors.forename: M
authors.initials: M
authors.lastname: Trucco
authors.forename: T W
authors.initials: TW
authors.lastname: Mak
mesh_terms: D000483:Alleles; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005260:Female; D006680:HLA Antigens / Q000032:analysis; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D008297:Male; D012150:Polymorphism, Restriction Fragment Length; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*
chemical_list: D006680:HLA Antigens; D006684:HLA-DR Antigens; D011948:Receptors, Antigen, T-Cell