HLA class II restriction of T helper cell response to cytomegalovirus (CMV). I. Immunogenetic control of restriction.

All three HLA class II families (DR, DQ, and DP) are involved in restriction of helper T cell (Th) recognition of nominal antigens including CMV. Only limited studies have been described previously to determine whether restricting determinants of DR and especially DQ are subtypic to the serologically defined DR and DQ specificities, and to what extent restricting determinants are associated with Dw specificities defined in alloresponses. In the present report, we describe a large number of CMV-specific Th clones derived from two different individuals who are seropositive for CMV. Clones were classified as being DR-, DQ-, or DP-reactive based on blocking with monoclonal antibodies. DR- and DQ-restricted clones were then examined in panel studies using antigen-presenting cells (APC) expressing the Dw subtype of the restricting DR-DQ haplotype, as well as APC expressing different Dw subtypes associated with the serologically defined specificity. Unrelated specificities were also included. Our findings show that not only for DR but for DQ as well, the primary restricting determinants appear to be subtypic to the serologically defined antigen; furthermore, subtype restriction for both DR and DQ is very closely associated with single Dw specificities. In several cases in which cross-reactivity among restricting Dw specificities was observed in association with a given DR or DQ haplotype, a molecular basis could be suggested to explain the cross-reacting determinants. A small minority of the clones appeared to be CMV specific, but was restricted by a determinant(s) that is either monomorphic or minimally polymorphic.