HLA class II restriction governing cell cooperation between antigen-specific helper T lymphocytes, B lymphocytes and monocytes for in vitro antibody production to influenza virus.

To study HLA class II compatibility requirement for in vitro antibody production to influenza virus, semipurified T lymphocytes, B lymphocytes and monocytes from HLA-typed responder donors were used. The presence of the three subpopulations was required for antibody production while a mixture of only two of those was ineffective. When using fresh T lymphocytes which exert an allogeneic suppressive effect and may also exhibit allogeneic helper activity, it was not possible to conclude an HLA class II-linked restriction of T-B cell cooperation although there was a suggestion of it. However, a grown H3 hemagglutinin-specific T cell line (L2), previously shown to be restricted by HLA-DR molecule (DR1) for interaction with antigen-presenting cells and devoid of allogeneic reactivity, exerts an HLA class II-restricted helper activity. This was demonstrated by various combinations of HLA-DR semi-compatible or incompatible B lymphocytes and/or monocytes with L2 T cells. The restriction element was identified as an HLA-DR determined since HLA-DC-compatible, HLA-DR-incompatible B lymphocytes were not helped by L2 T cells. In addition, monoclonal anti-HLA-DR but not anti-HLA-DC antibodies directed to the relevant specificity did inhibit the antigen-specific helper activity. We present evidence that not only T monocyte but also T-B and/or T-B-monocyte interactions are HLA class II restricted.