Allelic T-cell receptor alpha complexes have little or no influence on susceptibility to type 1 diabetes.
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.
Sheehy
M J
MJ
American Red Cross Blood Services, Madison, WI 53705.
Meske
L M
LM
Emler
C A
CA
Rowe
J R
JR
Neme de Gimenez
M H
MH
Ingle
C A
CA
Chan
A
A
Trucco
M
M
Mak
T W
TW
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*
D006680:HLA Antigens; D006684:HLA-DR Antigens; D011948:Receptors, Antigen, T-Cell