Correlation of Primary Sequence and Functional Determinants of HLA Class II Molecules

The structure-function relationship of HLA class II molecules remains one of the main areas of interest in HLA immunogenetics. While X-ray crystallographic studies are one ultimate goal, association of primary sequences of polymorphic genes with functional T lymphocyte-defined (LD) determinants represents a first approximation to this goal; our interpretations must be considered in that light. Data accumulating in two areas are of value in this regard. First, we and others (1–6) have provided DNA sequence information comparing polymorphic genes associated with Dw/LD subtype polymorphism of certain DR specificities. Second, we have used cloned T-cell reagents to define polymorphic epitopes associated with DR and DQ (7,8). We report here that sharing of amino acid (aa) sequences in the third, as well as possibly the second, hypervariable regions (HVR-aa 67–74 and aa 26–31) in several cases appears to correlate with sharing of LD epitopes.