Abstract
Spleen cells from H-2b,k,d C57Bl/10 congenic mice were sensitized in vitro to trinitrobenzenesulfonate (TNBS)-modified autologous spleen cells. Cold target competition studies at the lytic phase demonstrated three distinct patterns of cytotoxic responsiveness: (a) H-2b spleen cells generated approximately equivalent CTL responses against Kb and Db modified self products, (b) H-2d spleen cells generated preferential responses against Dd modified self products, and (c) H-2k spleen cells generated cytotoxic responses which could only be detected against Kk self products in association with TNP. F1 spleen cells were sensitized against autologous TNBS-treated cells. The results showed that, although H-2b parental cells generated approximately equivalent Kb-TNP- and Db-TNP-specific CTL, the presence of the H-2b haplotype did not result in the generation of (a) Dk-TNP CTL response by (H-2b x H-2k) spleen cells, nor (b) a Db CTL response by (H-2b x H-2a) F1 spleen cells. Additionally, (H-2d x H-2k) F1 cells failed to generate detectable Dd-TNP-specific CTL, although H-2d parental cells generated D-regional-specific CTL. The findings demonstrated that these F1 response patterns paralleled those of the H-2k and H-2a parents, i.e. weak or no D-region TNP-specific CTL were induced. Because (H-2d x H- 2a) F1 responders stimulated with H-2d TNBS-treated cells did generate good Dd TNP responses, the results illustrated that the presence of responder genes was not sufficient to result in a D-region TNP CML. It is suggested that the absence of Kk alleles on the stimulating population is necessary for the generation of D-region TNP CTL in these F1's. Mechanisms which could account for these response patterns in parental F1 mice are discussed including immunodominance, suppression, T-cell response , and Ir-gene defects.
Full Text
The Full Text of this article is available as a PDF (799.2 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bennink J. R., Doherty P. C. T-cell populations specifically depleted of alloreactive potential cannot be induced to lyse H-2-different virus-infected target cells. J Exp Med. 1978 Jul 1;148(1):128–135. doi: 10.1084/jem.148.1.128. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Blank K. J., Freedman H. A., Lilly F. T-lymphocytes response to Friend virus-induced tumour cell lines in mice of strains congenic at H--2. Nature. 1976 Mar 18;260(5548):250–252. doi: 10.1038/260250a0. [DOI] [PubMed] [Google Scholar]
- Claman H. N., Miller S. D., Moorhead J. W. Tolerance: two pathways of negative immunoregulation in contact sensitivity to DNFB. Cold Spring Harb Symp Quant Biol. 1977;41(Pt 1):105–111. doi: 10.1101/sqb.1977.041.01.014. [DOI] [PubMed] [Google Scholar]
- Doherty P. C., Biddison W. E., Bennink J. R., Knowles B. B. Cytotoxic T-cell responses in mice infected with influenza and vaccinia viruses vary in magnitude with H-2 genotype. J Exp Med. 1978 Aug 1;148(2):534–543. doi: 10.1084/jem.148.2.534. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Forman J. On the role of the H-2 histocompatibility complex in determining the specificity of cytotoxic effector cells sensitized against syngeneic trinitrophenyl-modified targets. J Exp Med. 1975 Aug 1;142(2):403–418. doi: 10.1084/jem.142.2.403. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gomard E., Duprez V., Reme T., Colombani M. J., Levy J. P. Exclusive involvement of H-2Db or H-2Kd product in the interaction between T-killer lymphocytes and syngeneic H-2b or H-2d viral lymphomas. J Exp Med. 1977 Oct 1;146(4):909–922. doi: 10.1084/jem.146.4.909. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pfizenmaier K., Trinchieri G., Solter D., Knowles B. B. Mapping of H-2 genes associated with T cell-mediated cytotoxic responses to SV40-tumour-associated specific antigens. Nature. 1978 Aug 17;274(5672):691–693. doi: 10.1038/274691a0. [DOI] [PubMed] [Google Scholar]
- Schmitt-Verhulst A. M., Shearer G. M. Bifunctional major histocompatibility-linked genetic regulation of cell-mediated lympholysis to trinitrophenyl-modified autologous lymphocytes. J Exp Med. 1975 Oct 1;142(4):914–927. doi: 10.1084/jem.142.4.914. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schmitt-Verhulst A. M., Shearer G. M. Multiple H-2 linked immune response gene control of H-2 D-associated T-cell-mediated lympholysis to trinitrophenyl-modified autologous cells: Ir-like genes mapping to the left of I-A and within the I region. J Exp Med. 1976 Dec 1;144(6):1701–1706. doi: 10.1084/jem.144.6.1701. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Scott D. W., Long C. A. Role of self-carriers in the immune response and tolerance. I. B-cell unresponsiveness and cytotoxic T-cell immunity induced by haptenated syngeneic lymphoid cells. J Exp Med. 1976 Nov 2;144(5):1369–1374. doi: 10.1084/jem.144.5.1369. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shearer G. M., Cudkowicz G. Induction of F1 hybrid antiparent cytotoxic effector cells: an in vitro model for hemopoietic histoincompatibility. Science. 1975 Nov 28;190(4217):890–893. doi: 10.1126/science.1188368. [DOI] [PubMed] [Google Scholar]
- Simpson E., Gordon R. D. Responsiveness to HY antigen Ir gene complementation and target cell specificity. Immunol Rev. 1977;35:59–75. doi: 10.1111/j.1600-065x.1977.tb00235.x. [DOI] [PubMed] [Google Scholar]
- Zinkernagel R. M., Althage A., Cooper S., Callahan G., Klein J. In irradiation chimeras, K or D regions of the chimeric host, not of the donor lymphocytes, determine immune responsiveness of antiviral cytotoxic T cells. J Exp Med. 1978 Sep 1;148(3):805–810. doi: 10.1084/jem.148.3.805. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zinkernagel R. M., Althage A., Cooper S., Kreeb G., Klein P. A., Sefton B., Flaherty L., Stimpfling J., Shreffler D., Klein J. Ir-genes in H-2 regulate generation of anti-viral cytotoxic T cells. Mapping to K or D and dominance of unresponsiveness. J Exp Med. 1978 Aug 1;148(2):592–606. doi: 10.1084/jem.148.2.592. [DOI] [PMC free article] [PubMed] [Google Scholar]