Contribution of direct and indirect recognition pathways to T cell alloreactivity.
T cells from an HLA-DR11/DR12 responder were stimulated in mixed lymphocyte culture with cells carrying the DR1 antigen. After priming, T cells proliferated in response to both DR1-positive-stimulating cells and a peptide derived from a polymorphic region of the HLA-DR beta 1*0101 chain presented by responder's antigen-presenting cells (APC). The dominant epitope recognized by the primed T cells corresponded to residue 21-42 and was presented by the responder's HLA-DR12 antigen. The DR1 peptide-reactive T cells express T cell receptor V beta 3. The results demonstrate that allopeptides derived from the processing and presentation of donor major histocompatibility complex molecules by host-derived APC trigger alloreactivity. The frequency of T cells engaged in the indirect pathway of allorecognition is about 100-fold lower than that of T cells participating in the direct recognition of native HLA-DR antigen. However, indirect allorecognition may play an important role in chronic allograft rejection, a phenomenon that is mediated by the activation of T helper cells and of alloantibody-producing B cells.
Liu
Z
Z
Department of Pathology, College of Physicians and Surgeons of Columbia University, New York, New York 10032.
Sun
Y K
YK
Xi
Y P
YP
Maffei
A
A
Reed
E
E
Harris
P
P
Suciu-Foca
N
N
D000483:Alleles; D002999:Clone Cells; D000939:Epitopes / Q000276:immunology; D006084:Graft Rejection; D006684:HLA-DR Antigens / Q000276:immunology*; D006801:Humans; D007114:Immunization; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*
D000939:Epitopes; D006684:HLA-DR Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta