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Visualizing Antigen Specific CD4+ T Cells using MHC Class II Tetramers
15:42

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Published on: March 6, 2009

Indirect allorecognition of HLA class I peptides by CD4+ cytolytic T lymphocytes

B Susskind1, M R Iannotti, M D Shornick

  • 1Division of Immunology and Organ Transplantation, University of Texas Health Science Center, Houston 77030, USA.

Human Immunology
|March 1, 1996
PubMed

T-cell responses to alloantigens can occur either by "direct" recognition of donor MHC molecules, or "indirect" recognition of MHC peptides in association with self-MHC. To evaluate human T cells mediating indirect allorecognition, a CD4+ TCL and clones specific for HLA-A1 or HLA-B8 (residues 60-84) were generated from normal PBLs (A2,29 B62,- DR1,4 DQ3). Most clones were A1 specific (16 out of 17 tested), HLA-DR4 restricted (8 out of 8), and lysed targets pulsed with A1 peptide (16 out of 16). An amino acid substitution at position 86 of the DR4 beta chain (G -> V) abrogated the capacity of CD4+ CTLs to lyse target cells. Chloroquine treatment of A1-pulsed targets reduced their susceptibility to lysis, indicating a requirement for peptide processing. The TCL and clones were stimulated to proliferate by cells bearing intact HLA-A1 when autologous APCs were present, indicating that the epitope contained within the A1 60-84 peptide being recognized is produced when APCs process native HLA-A1. Furthermore, the clones and TCL did not recognize HLA-A1 on target cells carrying this allele plus self-HLA-DR4. These studies suggest a much wider role for CD4+ T cells in allograft immunity.

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