Glenn E. Rodey

A public antigenic determinant in the HLA-B5 cross-reacting group— A basis for cross-reactivity and a possible link with Behcet's disease

Serologic cross-reactivity among allelic gene products commonly occurs in the HLA complex, but the molecular basis of these serologic phenomena is incompletely characterized. Because of strong cross-reactivity among antigens comprising the B5 cross-reactive group (i.e., HLA-B5, B15, B18, and Bw35), we initiated a study of the chemical basis of cross-reactivity among this group of antigens. Using classic serologic procedures, an 125I-Protein A binding assay, and chemical immunoprecipitation techniques, we have defined a new antigenic determinant, tentatively designated Y, which is present on certain HLA-B molecules. By a series of sequential immuno-precipitation experiments, Y was shown to be a public antigenic determinant distinct from the private determinants B5, B15, B18, and Bw35, but present on the same 44,000 dalton glycoprotein molecules. Although B5 is most highly associated with Behcets disease, other members of the B5 cross-reactive group have also been associated with Behcets, albeit to a lesser extent. These associations suggest that determinant Y may play a role in predisposition to Behcets disease.

HLA serological cross-reactivity: HLA-B15 has two public antigens.

On the basis of their serologic cross-reactivity, HLA antigens can be organized into cross-reactive groups or CREGs. We have recently defined immunochemically two public alloantigenic determinants X and Y which can account for the serological cross-reactivity of the B7-CREG and B5-CREG, respectively. One of the smaller of these CREGs consists of HLA-B15 and B17. Using microcytotoxicity testing, a fluoresceinated Protein A binding assay, and chemical immunoprecipitation techniques, we have defined a new public alloantigenic determinant, tentatively designated Z, which is present on the 44,000 dalton glycoprotein chains of HLA-B15 and HLA-B17, but distinct from the B15 and B17 determinants. Since HLA-B15 is also a member of the B5-CREG, and therefore bears allodeterminant Y, this report constitutes the first immunochemical demonstration of two public determinants, Y and Z, on a single HLA-B molecule, HLA-B15.