Polymorphic DQ alpha and DQ beta interactions dictate HLA class II determinants of allo-recognition.

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Abstract
18 transfected cell lines were generated that expressed distinct DQ molecules related to the serologically defined HLA-DWw3 specificity. These transfectants were constructed using site-directed mutagenesis to introduce nucleotide substitutions into DQ3.2.beta. cDNA, followed by retrovirus-mediated gene expression of the mutagenized genes in human B cell lines with different endogenous DQ.alpha. chains. The capacity of particular human class II dimers to stimulate alloreactive T cell clones was investigated. T cell activation was found to be dependent on both DQ.alpha. and DQ.beta. chains. In some cases, single amino acid substitutions at codons 13, 26, 45, or 57 of the DQ.beta. chain were sufficient to dramatically alter T cell reactivity; T cell recognition of these substitutions, however, was strongly influenced by the .alpha. chain polymorphisms present in the stimulatory class II dimer. Both gain and loss of major serologic and cellular specificities associated with specific DQw3+ alleles were observed with a limited array of site-directed substitutions.