HLA‐DR‐4‐associated alloreactivity of an HLA‐DR‐3‐ restricted human tetanus toxoid‐specific T cell clone: inhibition of both reactivities by an alloantiserum

Abstract

We present here the first report of a human helper/nducer T cell clone (F6) that specifically recognizes tetanus toxoid (IT) in the context of self‐major histocompati‐ bility complex (MHC) determinant(s) (HLA‐DR3), and in addition recognizes a specific but unrelated MHC determinant(s) in the absence of conventional antigen. Extensive subcloning insured that the cells were progeny of a single cell. Furthermore, removal of the cells proliferating to the alloantigen with bromodeoxyuridine and light removed cells responding to both TT plus self‐MHC and to the stimulating alloantigen, again indicating that F6 was the progeny of a single cell. The alloantigen recognized by this TT‐specific clone appears to be closely linked to HLA‐DR4 since cells from 13 of 14 HLA‐DR4⁺ donors stimulated F6. An antiserum which recognizes HLA‐DR4, when added to cultures, blocked the alloreactivity of F6, and in addition blocked its proliferation to 'IT plus HLA‐DR3. Absorption of this antiserum with HLA‐DR4⁺ cells or with IT‐pulsed HLA‐DR3⁺ cells removed its capacity to inhibit the proliferation of F6. These results suggest that the antigen recognition unit on F6 is stimulated both by allodeterminants expressed on HLA‐DR4 cells and by TT plus HLA‐DR3. These moieties cross‐react at the T cell recogni‐ tion level as well as at the antibody level.