Indirect allorecognition of HLA class I peptides by CD4+ cytolytic T lymphocytes.
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.
Susskind
B
B
Division of Immunology and Organ Transplantation, University of Texas Health Science Center, Houston 77030, USA.
Iannotti
M R
MR
Shornick
M D
MD
Steward
N S
NS
Gorka
J
J
Mohanakumar
T
T
D017951:Antigen Presentation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D002999:Clone Cells / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D006084:Graft Rejection; D006680:HLA Antigens / Q000276:immunology*; D015788:HLA-A1 Antigen / Q000276:immunology; D015795:HLA-B8 Antigen / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology; D015804:HLA-DR4 Antigen / Q000276:immunology; D059811:HLA-DRB1 Chains; D006801:Humans; D008213:Lymphocyte Activation; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D006680:HLA Antigens; D015788:HLA-A1 Antigen; D015795:HLA-B8 Antigen; D006684:HLA-DR Antigens; D015804:HLA-DR4 Antigen; D059811:HLA-DRB1 Chains; D010446:Peptide Fragments