Journal of Experimental Medicine, Vol 158, 1537-1546, Copyright © 1983 by Rockefeller University Press

ARTICLES

Cytotoxic T lymphocyte nonresponsiveness to the male antigen H-Y in the H-2Db mutants bm13 and bm14. Complementation of the response in F1 crosses with the I-Ab mutant bm12 nonresponder and failure of B6 or Db mutant mice tolerant of each other to respond to allogeneic male cells

LP De Waal, RW Melvold and CJ Melief

The cytotoxic T-lymphocyte (CTL) response against the male-specific antigen H-Y in C57BL/6 (B6, H-2b) mice is regulated by the I-Ab and Db molecules. From previous studies, we concluded that the bm12 I-Ab mutant does not respond to H-Y, because of a deletion in its T-helper- cell repertoire. We now demonstrate that two Db mutants, bm13 and bm14, also fail to generate a CTL response to H-Y. The bm12 class-II mutant on one hand and the bm13 and bm14 class-I mutants on the other complemented each other for the H-Y-specific CTL response in (bm12 X bm13)F1 and (bm 12 X bm 14)F1 hybrids. This indicates that the need for tolerance of the mutant class II and class I molecules in these hybrids does not create deletions in the I-Ab-restricted T helper cell and Db- restricted CTL repertoire for H-Y. This study constitutes the first demonstration with H-2 mutants that a CTL response controlled by class I and class II MHC molecules is complemented in an F1 cross between a class I and a class II nonresponder. (B6 X bm 13)F1 and (B6 X bm 14)F1 hybrids only responded to H-Y when the antigen was presented on F1 or B6 antigen-presenting cells (apc) but not on Db mutant apc. B6 or Db mutant responders rendered neonatally tolerant of each other failed to respond to the H-Y antigen presented on the tolerogenic allogeneic cell. In the tolerized animals, a response was only seen with responder (B6) type T cells and responder type (B6) apc, indicating that both the T cell source and the MHC type of the apc have to be taken into account in this system. Thus, Ir genes may act at the level of both the T cell repertoire and antigen presentation.
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This article has been cited by other articles:

• Peterson, K. E., Iwashiro, M., Hasenkrug, K. J., Chesebro, B. (2000). Major Histocompatibility Complex Class I Gene Controls the Generation of Gamma Interferon-Producing CD4+ and CD8+ T Cells Important for Recovery from Friend Retrovirus-Induced Leukemia. J. Virol. 74: 5363-5367 [Abstract] [Full Text]  

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