Mouse cytolytic T lymphocytes induced by xenogeneic rat stimulator cells exhibit specificity for H-2 complex alloantigens.

Burakoff, Steven J.; Ratnofsky, Sheldon; Benacerraf, Baruj

doi:10.1073/pnas.74.10.4572

Cited by 28 publications

(12 citation statements)

References 16 publications

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“…has been shown to be restricted entirely to recognition of the MHC products on the stimulator cells (1)(2)(3). Similar to allogeneic and MHC-restricted responses, proliferative responses to xenogeneic class II MHC are generally mediated by CD4 + lymphocytes (4,5), whereas CTL responses to xenogeneic class I molecules are mediated by CD8 + cells (5,6).…”

Section: T He Response Of T Cells Of One Species To Cells Of Anothermentioning

confidence: 99%

“…Similar to allogeneic and MHC-restricted responses, proliferative responses to xenogeneic class II MHC are generally mediated by CD4 + lymphocytes (4,5), whereas CTL responses to xenogeneic class I molecules are mediated by CD8 + cells (5,6). Such responses are directed against "alloantigenic" determinants rather than to species-specific epitopes as demonstrated by the predominant response of xenogeneic T cells to polymorphic determinants of the MHC antigens of another spedes (1,2,5,(7)(8)(9)(10)(11). However, murine T cell responses to human class I (12,13) and class II molecules (2)(3)(4)14) are one to two orders of magnitude lower than responses against allogeneic MHC molecules.…”

Section: T He Response Of T Cells Of One Species To Cells Of Anothermentioning

confidence: 99%

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Species specificity and augmentation of responses to class II major histocompatibility complex molecules in human CD4 transgenic mice.

Barzaga-Gilbert

Grass

Lawrance

et al. 1992

The Journal of Experimental Medicine

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Sllmmal'yMurine T cell responses to human class II major histocompatibility complex (MHC) molecules were shown to be a minimum of 20-70-fold lower than responses to allogendc molecules. Transgenic mice expressing slightly below normal (75-95%) or very high (250-380%) cell surface levels of human CD4 were utilized to determine whether this was due to a species-specific interaction between murine CD4 and class II molecules. Human CD4 was shown to function in signal transduction events in murine T cells based on the ability of anti-human CD4 antibody to synergize with suboptimal doses of anti-murine CD3 antibody in stimulating T cell proliferation. In mice expressing lower levels of human CD4, T cell responses to human class II molecules were enhanced up to threefold, whereas allogeneic responses were unaltered. In mice expressing high levels of human CD4, responses to human class II molecules were enhanced at least 10-fold, whereas allogeneic responses were between one and three times the level of normal responses. The relatively greater enhancement of the response to human class II molecules in both lines argues for a preferential interaction between human CD4 and human class II molecules. In mice expressing lower levels of human CD4, responses to human class II molecules were blocked by antibodies to CD4 of either species, indicating participation by both molecules. In mice expressing high levels of human CD4, responses to both human and murine class II molecules were almost completely blocked with anti-human CD4 antibody, whereas anti-routine CD4 antibody had no effect. However, anti-routine CD4 continued to synergize with anti-CD3 in stimulating T cell proliferation in these mice. Thus, overexpression of human CD4 selectively impaired the ability of murine CD4 to assist in the process of antigen recognition. The ability of human CD4 to support a strong allogeneic response under these conditions indicates that this molecule can interact with murine class II molecules to a significant extent. Despite the fact that human CD4 appeared to be the only functional coreceptor in these mice, responses to human class II molecules were still much lower than those to murine class II alloantigens. This indicates that species-specific interactions between class II molecules and CD4 expressed on peripheral T cells are not suf~cient to account for the low xenogeneic response and that intrinsic differences in T cell receptor structures or the need for species specificity in the interaction between CD4 and class II molecules during positive selection are also important. The response of T cells of one species to cells of another has been shown to be restricted entirely to recognition of the MHC products on the stimulator cells (1-3). Similar to allogeneic and MHC-restricted responses, proliferative responses to xenogeneic class II MHC are generally mediated by CD4 + lymphocytes (4, 5), whereas CTL responses to xenogeneic class I molecules are mediated by CD8 + cells (5,6). Such responses are directed against "alloantigenic" deter...

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Section: T He Response Of T Cells Of One Species To Cells Of Anothermentioning

confidence: 99%

Section: T He Response Of T Cells Of One Species To Cells Of Anothermentioning

confidence: 99%

Species specificity and augmentation of responses to class II major histocompatibility complex molecules in human CD4 transgenic mice.

Barzaga-Gilbert

Grass

Lawrance

et al. 1992

The Journal of Experimental Medicine

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“…This is at variance with what we and others have previously reported on the generation of human CTL following a single in vitro exposure to normal mouse spleen cells [6, 71. Such an interspecies dyssymmetry in T cell recognition may reflect an evolutionary process within the MHC system whereby the mouse T cell repertoire, still capable of discriminating between the various rat MHC allotypes [13], is no longer capable of recognizing with high efficiency the xenoantigens and, in particuliar, the MHC determinants carried by human cells. As recently illustrated, increasing the phylogenetic distance can not only affect the strength of the immune response but more drastically, the nature of the recognized epitopes [14].…”

Section: Discussionmentioning

confidence: 99%

Education of mouse lymphocytes against human lymphoblastoid cell lines: Specific recognition of determinants independent of serologically defined HLA allotypes and Epstein‐Barr virus‐coded antigens

1979

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In this report, a model of xenogeneic education is described, whereby cytotoxic mouse spleen cells are generated against human target cell antigens. To generate a significant response, a primary in vivo immunization followed by an in vitro boosting 4 to 8 weeks later is required. Lysis is totally abrogated after treatment of the effector cells by anti-Thy-1.2 antiserum plus complement confirming the T origin of these effectors. Such cytotoxic T lymphocytes (CTL) do not discriminate between two lymphoblastoid cell lines carrying different HLA-A and HLA-B specificities, either by direct assay or by competition assay with unlabeled target cells. Moreover, Daudi cells which lack the serologically defined (SD) HLA antigens, are susceptible to CTL specifically raised against Daudi. However, CTL raised against another B line do not lyse Daudi, and, reciprocally, anti-Daudi CTL do not lyse other B lines thus suggesting a polymorphic distribution of xenogeneic determinants on human lymphoid lines. A third specificity is revealed when mouse spleen cells are educated against human T lines. The CTL generated under these conditions lyse not only the line used for sensitization but the three other human T lines of the panel. On the other hand, they affect none of the B cell lines (including Daudi) nor phytohemagglutinin or concanavalin A-induced T blasts. In conclusion, the mouse T cell repertoire is capable of recognizing a polymorphic system of antigens expressed on human lymphoblastoid cell lines that is not related to the expression of HLA-SD antigens nor to that of the Epstein-Barr virus genome.

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“…The augmenting effects observed in the present study can be explained most naturally by cross-reactivities between cells used for presensitization, in vitro sensitization and cytotoxicity assay since cross-reactivity was reported to exist even in a xenogeneic combination between mice and rats (4). Mechanisms of the effects will be analyzed in a series of studies along the lines in this paper.…”

Section: Effects Of Donor Strains Of Responding Cells On In Vivo Indumentioning

confidence: 99%

Effects of In Vivo Priming on In Vitro Induction of Cytotoxicity

Yamada

Nomoto

Takeya

1979

Microbiology and Immunology

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Mouse cytolytic T lymphocytes induced by xenogeneic rat stimulator cells exhibit specificity for H-2 complex alloantigens.

Cited by 28 publications

References 16 publications

Species specificity and augmentation of responses to class II major histocompatibility complex molecules in human CD4 transgenic mice.

Species specificity and augmentation of responses to class II major histocompatibility complex molecules in human CD4 transgenic mice.

Education of mouse lymphocytes against human lymphoblastoid cell lines: Specific recognition of determinants independent of serologically defined HLA allotypes and Epstein‐Barr virus‐coded antigens

Effects of In Vivo Priming on In Vitro Induction of Cytotoxicity

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