Protection from T helper cell-mediated graft-versus-host disease by the presence of an MHC class I alloantigen is associated with perturbation of MHC class II-restricted responses by class I-derived peptides

Ramona R. Leibnitz, Peter E. Lipsky, Dwain L Thiele

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Abstract

Lethal graft-vs-host disease (GVHD) develops after transfer of CTL-depleted spleen and bone marrow cells from C57BL/6 (B6) mice to irradiated MHC class II disparate (B6×bm12)F1 recipients. Onset of lethal GVHD is significantly delayed in (bm1×bm12)F1 recipients of the same donor inoculum despite the additional MHC class I disparity (H-2Kbm1). To investigate the basis of this protective effect, hybridomas were generated from T cells activated in vivo during GVHD in both strain combinations. T cells from B6→(B6×bm12)F1 mice generated a significantly higher frequency of B6.C-H-2bm12 (bm12)-specific T hybridomas (110/178, 62%) than T cells from B6→(bm1→bm12)F1 mice (102/218, 47%). Some bm12-specific T hybridomas exhibited lesser responses to (bm1×bm12)F1 than to (B6×bm12)F1 APC. Moreover, bm1 peptides spanning a 14-amino acid region that includes the three amino acids that differ from H-2Kb were found to inhibit responses of some bm12-specific T hybridomas and to decrease significantly responses of splenic B6 CD4+ T cells to bm12 APC. Notably, the frequency of bm12-reactive hybridomas susceptible to inhibition by bm1 peptides generated from B6→(B6×bm12)F1 mice was significantly greater than that generated from B6→(bm1×bm12)F1 mice. Additional analysis using L cell transfectants indicated that hybridomas responding to the bm12 mutation at position 70 alone were rarely inhibited by bm1 peptides. The data indicate that expression of bm1-derived peptides can influence the frequency and spec-ificity of alloreactive CD4+ T cells stimulated in vivo and thus may alter the course of GVHD.

Original languageEnglish (US)
Pages (from-to)1784-1795
Number of pages12
JournalJournal of Immunology
Volume155
Issue number4
StatePublished - 1995

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Isoantigens
Hybridomas
Graft vs Host Disease
Helper-Inducer T-Lymphocytes
Peptides
T-Lymphocytes
Amino Acids
Bone Marrow Cells
Spleen
Mutation

ASJC Scopus subject areas

  • Immunology

Cite this

@article{6aa885e9604d4946b852f262cde60453,
title = "Protection from T helper cell-mediated graft-versus-host disease by the presence of an MHC class I alloantigen is associated with perturbation of MHC class II-restricted responses by class I-derived peptides",
abstract = "Lethal graft-vs-host disease (GVHD) develops after transfer of CTL-depleted spleen and bone marrow cells from C57BL/6 (B6) mice to irradiated MHC class II disparate (B6×bm12)F1 recipients. Onset of lethal GVHD is significantly delayed in (bm1×bm12)F1 recipients of the same donor inoculum despite the additional MHC class I disparity (H-2Kbm1). To investigate the basis of this protective effect, hybridomas were generated from T cells activated in vivo during GVHD in both strain combinations. T cells from B6→(B6×bm12)F1 mice generated a significantly higher frequency of B6.C-H-2bm12 (bm12)-specific T hybridomas (110/178, 62{\%}) than T cells from B6→(bm1→bm12)F1 mice (102/218, 47{\%}). Some bm12-specific T hybridomas exhibited lesser responses to (bm1×bm12)F1 than to (B6×bm12)F1 APC. Moreover, bm1 peptides spanning a 14-amino acid region that includes the three amino acids that differ from H-2Kb were found to inhibit responses of some bm12-specific T hybridomas and to decrease significantly responses of splenic B6 CD4+ T cells to bm12 APC. Notably, the frequency of bm12-reactive hybridomas susceptible to inhibition by bm1 peptides generated from B6→(B6×bm12)F1 mice was significantly greater than that generated from B6→(bm1×bm12)F1 mice. Additional analysis using L cell transfectants indicated that hybridomas responding to the bm12 mutation at position 70 alone were rarely inhibited by bm1 peptides. The data indicate that expression of bm1-derived peptides can influence the frequency and spec-ificity of alloreactive CD4+ T cells stimulated in vivo and thus may alter the course of GVHD.",
author = "Leibnitz, {Ramona R.} and Lipsky, {Peter E.} and Thiele, {Dwain L}",
year = "1995",
language = "English (US)",
volume = "155",
pages = "1784--1795",
journal = "Journal of Immunology",
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T1 - Protection from T helper cell-mediated graft-versus-host disease by the presence of an MHC class I alloantigen is associated with perturbation of MHC class II-restricted responses by class I-derived peptides

AU - Leibnitz, Ramona R.

AU - Lipsky, Peter E.

AU - Thiele, Dwain L

PY - 1995

Y1 - 1995

N2 - Lethal graft-vs-host disease (GVHD) develops after transfer of CTL-depleted spleen and bone marrow cells from C57BL/6 (B6) mice to irradiated MHC class II disparate (B6×bm12)F1 recipients. Onset of lethal GVHD is significantly delayed in (bm1×bm12)F1 recipients of the same donor inoculum despite the additional MHC class I disparity (H-2Kbm1). To investigate the basis of this protective effect, hybridomas were generated from T cells activated in vivo during GVHD in both strain combinations. T cells from B6→(B6×bm12)F1 mice generated a significantly higher frequency of B6.C-H-2bm12 (bm12)-specific T hybridomas (110/178, 62%) than T cells from B6→(bm1→bm12)F1 mice (102/218, 47%). Some bm12-specific T hybridomas exhibited lesser responses to (bm1×bm12)F1 than to (B6×bm12)F1 APC. Moreover, bm1 peptides spanning a 14-amino acid region that includes the three amino acids that differ from H-2Kb were found to inhibit responses of some bm12-specific T hybridomas and to decrease significantly responses of splenic B6 CD4+ T cells to bm12 APC. Notably, the frequency of bm12-reactive hybridomas susceptible to inhibition by bm1 peptides generated from B6→(B6×bm12)F1 mice was significantly greater than that generated from B6→(bm1×bm12)F1 mice. Additional analysis using L cell transfectants indicated that hybridomas responding to the bm12 mutation at position 70 alone were rarely inhibited by bm1 peptides. The data indicate that expression of bm1-derived peptides can influence the frequency and spec-ificity of alloreactive CD4+ T cells stimulated in vivo and thus may alter the course of GVHD.

AB - Lethal graft-vs-host disease (GVHD) develops after transfer of CTL-depleted spleen and bone marrow cells from C57BL/6 (B6) mice to irradiated MHC class II disparate (B6×bm12)F1 recipients. Onset of lethal GVHD is significantly delayed in (bm1×bm12)F1 recipients of the same donor inoculum despite the additional MHC class I disparity (H-2Kbm1). To investigate the basis of this protective effect, hybridomas were generated from T cells activated in vivo during GVHD in both strain combinations. T cells from B6→(B6×bm12)F1 mice generated a significantly higher frequency of B6.C-H-2bm12 (bm12)-specific T hybridomas (110/178, 62%) than T cells from B6→(bm1→bm12)F1 mice (102/218, 47%). Some bm12-specific T hybridomas exhibited lesser responses to (bm1×bm12)F1 than to (B6×bm12)F1 APC. Moreover, bm1 peptides spanning a 14-amino acid region that includes the three amino acids that differ from H-2Kb were found to inhibit responses of some bm12-specific T hybridomas and to decrease significantly responses of splenic B6 CD4+ T cells to bm12 APC. Notably, the frequency of bm12-reactive hybridomas susceptible to inhibition by bm1 peptides generated from B6→(B6×bm12)F1 mice was significantly greater than that generated from B6→(bm1×bm12)F1 mice. Additional analysis using L cell transfectants indicated that hybridomas responding to the bm12 mutation at position 70 alone were rarely inhibited by bm1 peptides. The data indicate that expression of bm1-derived peptides can influence the frequency and spec-ificity of alloreactive CD4+ T cells stimulated in vivo and thus may alter the course of GVHD.

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M3 - Article

VL - 155

SP - 1784

EP - 1795

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

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