T cell recognition of QA-1b antigens on cells lacking a functional Tap-2 transporter.

CJ Aldrich, R Waltrip, E Hermel, M Attaya… - … (Baltimore, Md.: 1950 …, 1992 - journals.aai.org
CJ Aldrich, R Waltrip, E Hermel, M Attaya, KF Lindahl, JJ Monaco, J Forman
Journal of immunology (Baltimore, Md.: 1950), 1992journals.aai.org
MHC class Ia H chains and beta 2-microglobulin assemble with appropriate peptides to form
stable cell surface molecules that serve as targets for Ag-specific CTL. The structural
similarities of class Ia and the less polymorphic Q/T/M (class Ib) molecules suggest that class
Ib molecules also play a role in antigen presentation, although the origin of the peptides they
present remains mostly unclear. The cell line RMA-S has a defect in class I Ag presentation,
presumably due to a mutation in a peptide transporter gene. This defect can be overcome by …
Abstract
MHC class Ia H chains and beta 2-microglobulin assemble with appropriate peptides to form stable cell surface molecules that serve as targets for Ag-specific CTL. The structural similarities of class Ia and the less polymorphic Q/T/M (class Ib) molecules suggest that class Ib molecules also play a role in antigen presentation, although the origin of the peptides they present remains mostly unclear. The cell line RMA-S has a defect in class I Ag presentation, presumably due to a mutation in a peptide transporter gene. This defect can be overcome by transfection of RMA-S cells with the Tap-2 gene (formerly Ham-2) that encodes an ATP-binding transporter protein. We now show that a substantial portion of alloreactive CTL specific for Qa-1 class Ib molecules recognize Qa-1b on RMA-S cells and thus differ from most class Ia specific CTL. Those anti-Qa-1b CTL that do not recognize untransfected RMA-S do lyse RMA-S transfected with Tap-2. We also examine the effects of Qdm, a gene that maps to the D region and alters recognition of Qa-1. Qdm(k) strains lack an epitope(s) recognized by some (Qdm dependent) anti-Qa-1 CTL whereas Qdm+ strains express this epitope. Thus, Qdm-dependent CTL do not recognize Qa-1 on Qdm(k) targets whereas Qdm-independent CTL recognize Qa-1 epitopes in all strains. Although Qdm-independent CTL varied as to whether they recognized RMA-S vs RMA, all nine Qdm-dependent clones only recognized Qa-1b on RMA and not RMA-S. This result is consistent with Qdm encoding a peptide dependent upon the TAP transporter for cell membrane expression.
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