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R Langman

Publications and source records attributed to R Langman.

6 recordsLinked to original sources
PubMed1992

Is the establishing of tolerance to self obligatorily MHC restricted?

The prevailing paradigm used to interpret how T cells recognize antigen treats antigen processing as obligatory because the T cell antigen receptor complex can only detect antigen located in a "groove" found on MHC-encoded restricting elements. The vast majority of experimental systems used to analyze how T cells recognize antigen depend on induced T cells executing their effector functions, and it is agreed without exception that this event is MHC restricted. However, to date, the extrapolation of the obligatory MHC restriction of effector function to the level of the antigen-responsive T cell that makes the tolerance induction decision, depends not on experiment, but on theoretical constructs. The few experiments designed to test whether tolerance is MHC restricted are open to several interpretations, only one of which is consistent with the view that all antigen recognition events must be MHC restricted. If it can be shown that tolerance is not obligatorily MHC restricted, then the pillar of the prevailing paradigm will have fallen. The experiments described here throw into serious doubt the evidence that has been used to conclude that tolerance is obligatorily MHC restricted.

Animals↗
PubMed1992

The priming of cytotoxic T-cell precursors is strictly helper T cell-dependent.

Allogeneic chimaeras that utilize C.B-17 SCID mice (H-2d) as recipients of MHC mismatched bone marrow from C57B1/6 (H-2b) or SJL/J (H-2s) mice have been used to provide experimental evidence demonstrating the necessity for a direct interaction between an effector T helper and the cytotoxic T-cell precursor in order to generate cytotoxic effector T cells specific for the minor histocompatibility (H) antigens of DBA/2 (H-2d) mice. No effect of helpers specific for antigen-processed or not-presented on antigen-presenting cells could be observed. Allo-chimaeras that contain T cells bearing H-2s, and which are restricted to H-2d, make a cytotoxic T-cell response to minor H antigens which is H-2d restricted if, and only if, cloned anti-H-2s effector T helpers are present during the in vivo priming step. Cloned anti-H-2d effector helpers, which are without effect in the allo-chimaeras, do provide a strong helper activity when tested in normal H-2d mice. These findings cannot be reconciled with a strict single recognitive model of restrictive antigen recognition, but they are consistent with a dual recognitive model, which incorporates many of the features of the single recognitive model.

Animals↗