Distinct T cell interactions with HLA class II tetramers characterize a spectrum of TCR affinities in the human antigen-specific T cell response.
The polyclonal nature of T cells expanding in an ongoing immune response results in a range of disparate affinities and activation potential. Recently developed human class II tetramers provide a means to analyze this diversity by direct characterization of the trimolecular TCR-peptide-MHC interaction in live cells. Two HSV-2 VP16(369-379)-specific, DQA1*0102/DQB1*0602 (DQ0602)-restricted T cell clones were compared by means of T cell proliferation assay and HLA-DQ0602 tetramer staining. These two clones were obtained from the same subject, but show different TCR gene usage. Clone 48 was 10-fold more sensitive to VP16(369-379) peptide stimulation than clone 5 as assayed by proliferation assays, correlating with differences in MHC tetramer binding. Clone 48 gave positive staining with the DQ0602/VP16(369-379) tetramer at either 23 or 37 degrees C. Weak staining was also observed at 4 degrees C. Clone 5 showed weaker staining compared with clone 48 at 37 degrees C, and no staining was observed at 23 degrees C or on ice. Receptor internalization was not required for positive staining. Competitive binding indicates that the cell surface TCR of clone 48 has higher affinity for the DQ0602/VP16(369-379) complex than clone 5. The higher binding affinity of clone 48 for the peptide-MHC complex also correlates with a slower dissociation rate compared with clone 5.
Reichstetter
S
S
Virginia Mason Research Center and University of Washington School of Medicine, Seattle, WA 98101, USA.
Ettinger
R A
RA
Liu
A W
AW
Gebe
J A
JA
Nepom
G T
GT
Kwok
W W
WW
D000595:Amino Acid Sequence; D017951:Antigen Presentation; D002450:Cell Communication / Q000276:immunology*; D002460:Cell Line; D002999:Clone Cells; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism*; D006683:HLA-DQ Antigens / Q000276:immunology / Q000378:metabolism*; D017405:Herpes Simplex Virus Protein Vmw65 / Q000378:metabolism; D018258:Herpesvirus 2, Human / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation; D008560:Membrane Fluidity / Q000276:immunology; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism*; D012680:Sensitivity and Specificity; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*
D018984:Epitopes, T-Lymphocyte; D006683:HLA-DQ Antigens; D017405:Herpes Simplex Virus Protein Vmw65; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell