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Human anti-porcine xenogeneic T cell response. Evidence for allelic specificity of mixed leukocyte reaction and for both direct and indirect pathways of recognition.

K Yamada, D H Sachs and H DerSimonian
J Immunol December 1, 1995, 155 (11) 5249-5256;
K Yamada
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D H Sachs
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H DerSimonian
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Abstract

Partially inbred, MHC homozygous miniature swine have been used to study the nature of the human xenogeneic cellular immune response to swine Ags in vitro. Human T cells responded to xeno-MHC Ags in MLR at least as well as they did to allo-MHC Ags and appeared to share similar requirements for APC of either stimulator (direct pathway) or responder (indirect pathway) derivation. In addition, mAb-blocking experiments indicated that the majority of the primary human anti-pig xeno-response was directed toward porcine MHC class II Ags and involved interaction with the human CD4 accessory molecule. Finally, the availability of intra-MHC recombinant haplotypes in our herds has made it possible to map genetically the antigenic specificities recognized in human anti-swine cellular responses. For this purpose, T cell clones were generated from human anti-swine MLR cultures and were tested for reactivity to stimulator cells from MHC homozygous and recombinant haplotypes. Clear evidence for antixenogeneic MHC Ags was observed. In all cases in which allelic differences between haplotypes were detected (the majority of clones), the reactivity could be mapped to the class II region of stimulator haplotypes. In addition, cross-reactivity between haplotypes was consistent with known sequence similarities between DR beta-chains. Our results indicate, therefore, that the human anti-porcine T cell response is similar in strength and specificity to an allogeneic response, and that the TCR repertoire, accessory molecule interactions, and cytokine production required for both direct and indirect pathways of recognition in the human anti-porcine MHC class II responses are functionally intact.

  • Copyright © 1995 by American Association of Immunologists

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The Journal of Immunology
Vol. 155, Issue 11
1 Dec 1995
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Human anti-porcine xenogeneic T cell response. Evidence for allelic specificity of mixed leukocyte reaction and for both direct and indirect pathways of recognition.
K Yamada, D H Sachs, H DerSimonian
The Journal of Immunology December 1, 1995, 155 (11) 5249-5256;

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Human anti-porcine xenogeneic T cell response. Evidence for allelic specificity of mixed leukocyte reaction and for both direct and indirect pathways of recognition.
K Yamada, D H Sachs, H DerSimonian
The Journal of Immunology December 1, 1995, 155 (11) 5249-5256;
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Print ISSN 0022-1767        Online ISSN 1550-6606