HETEROGENEOUS MHC-II RESTRICTION PATTERN OF AUTOREACTIVE DESMOGLEIN-3SPECIFIC T-CELL RESPONSES IN PEMPHIGUS-VULGARIS PATIENTS AND NORMALS

Pemphigus vulgaris is a life threatening bullous autoimmune disease of the skin mediated by autoantibodies against desmoglein 3 (Dsg3) on ep idermal keratinocytes. Pemphigus vulgaris patients exhibit T cell resp onses against Dsg3 that may serve as a target to modulate the producti on of pathogenic autoantibodies. Healthy carriers of major histocompat ibility complex class II alleles identical or similar to those that ar e highly prevalent in pemphigus vulgaris, namely DR beta 10402 and DR beta 11401, also mount T cell responses against Dsg3. We thus wanted to determine whether these prevalent major histocompatibility complex class II alleles restricted Dsg3 specific T cell responses. A CD4(+) T cell line ti om the DR beta 10402(+) patient PV9 was stimulated by Dsg3 with DR beta 10402(+) L cells as antigen-presenting cells, A CD4 (+) T cell line and six CD4(+) T cell clones from the DR11/14(+) patie nt PV8, and six CD4(+) T cell clones from the DR11(+) healthy donor C6 , required DR11/DQ beta 10301(+) peripheral blood mononuclear cells b ut not DR11(+) L cells as antigen-presenting cells and were strongly i nhibited by anti-Dq antibodies, indicating that they were restricted b y HLA-DQ beta 10301. A CD4(+) T cell line and three T cell clones fro m the DR11(+) healthy donor C11 were differentially stimulated by Dsg3 with L cells expressing one of several DR11 alleles, T cell recogniti on of Dsg3 was thus not only restricted by the pemphigus vulgaris asso ciated DR beta 10402 allele, but also by several DR11 alleles, some o f which are highly homologous to DR beta 1-0402, and by HLA-DQ beta 1 0301.