Development of class I-specific helper-inducer T-cell clone.

Abstract

A unique alloreactive human helper-inducer T-cell clone which reacts with the class I HLA antigen was characterized. The clone was derived from a mixed lymphocyte culture between cells from a HLA-A2-; B35,w51; Bw4,Bw6; Cw4,-; DR1,4; DQw1,-; DRw53 responder and a HLA-A2,3; B7,14; Bw6; Cw8,-; DR7,-; DQw2,w3; DRw52 stimulator. When screened against a panel of stimulator cells, this clone was found to have a specificity towards a stimulator HLA-B14 and consisted entirely of Leu-4, Leu-3, and 4B4 positive T cells, which is a T helper-inducer phenotype. Using monoclonal antibodies directed towards various monomorphic class I and II HLA epitopes in an inhibition experiment, it was found that both monoclonal antibodies w6/32 and 4E (recognizing class I monomorphic and HLA-B epitopes, respectively) inhibited proliferation. However, monoclonal antibodies BBm.1 and L227 (directed against beta 2-microglobulin and Ia-like molecule, respectively) had no inhibitory effect. Functional evaluation of this clone demonstrated helper activity on the proliferation of MLC response. The helper-induction effect on MLC cultures remained intact following irradiation of the clone for either 500 or 2000 rad suggesting that helper function of the clone was radiation resistant. The helper activity of this clone was MHC nonrestricted since it enhanced proliferation of the original responder and stimulator MLC as well as third and fourth party individuals. By CTLL cell line proliferation assay, this clone was found to release IL-2. When assayed (day 1 to 7) for class II HLA products expression following stimulation, HLA-DRw53 was consistently expressed by the clone. However, HLA-DR1, DQw1 were found to be expressed simultaneously on day 2 through day 7 and HLA-DR4, DQw3 on day 2 and 3. These data demonstrate, for the first time, the generation of a class I specific helper-inducer T-cell clone in MLC response.