Clones of cytotoxic lymphocytes can recognise uninfected cells in a primary response against influenza virus

Abstract

THE specificity of cytotoxic T lymphocytes against influenza virus-infected target cells has been investigated in primary responses in vivo1–5 and in secondary responses both in vivo1 and in vitro2,4,6. Cold target inhibition techniques have been used to analyse the specificity of responses but this approach has not produced total agreement between all workers2,3,5,6. By analogy with antibody production, the most effective way of analysing the specificity of a response is to assess the specificity of a representative sample of monoclonal cytotoxic lymphocytes (CL). To this end we have devised culture conditions whereby individual clones of CL may be generated in a primary antiviral response against influenza A-infected cells. Our work shows that a clonal analysis of virus-induced cytotoxic T cells is feasible. The analysis of individual clones will allow any cross-reactivity towards cells infected with different strains of virus, for example, to be attributed to cross-reactive clones or the existence of several clones each with unique specificity. We report here that in establishing this approach, we have detected several clones which lyse uninfected target cells and we have studied the time of appearance of such clones.