Correlated mutations in the HLA class II molecule

A correlated mutation analysis was performed on aligned sequences of the hu man leukocyte antigen (HLA) HLA-DR, HLA-DP, and HLA-DQ class II receptors w ith a view to understanding their molecular associations, particularly thos e involving their alpha and beta domains. The analysis was carried out on 2 3 HLA-DR alleles, 12 DP alleles, and 24 DQ alleles; the analysis was also c arried out on the global alignment of the DR, DP, and DQ alleles. These ana lyses identified 13, 18, 26, and 27 correlated mutations, respectively. Bet ween 72 and 85% of the correlated mutations were found to occur at domain i nterfaces within the alpha or beta chain, at the interface of the alpha bet a heterodimer, or at the interface of the (alpha beta)(2) dimer of heterodi mers. These results are discussed in the light of recent results that have shown that the HLA class II receptor forms temperature-dependent dimers of dimers on the surface of living cells. (C) 1999 John Wiley & Sons, Inc. Int J Quant Chem 73: 85-96, 1999.