Influence of CD26 and integrins on the antigen sensitivity of human memory T cells.
The antigen sensitivity of class II MHC restricted human CD4 T-cell clones is demonstrated to increase gradually with time after restimulation. This is manifested in a requirement of less antigen in culture, as well as decreased numbers of peptide-MHC complexes per APC for T-cell activation, and in an increased resistance to inhibition by class II MHC blockade. The increase in antigen sensitivity is accompanied by increased cell-surface expression of CD26, LFA-1, and VLA-1, whereas the expression of TCR and a series of other cell-surface molecules remains unchanged. Using appropriate monoclonal antibodies, we have shown that CD26 and LFA-1 contribute directly to the increased antigen sensitivity of "late-stage" T-cell clones. The late-memory T-cell phenotype established in this study is shown to occur also among T cells activated in vivo. We suggest that increasing the antigen sensitivity via antigen-nonspecific molecules is a physiologic mechanism for maintaining T-cell memory in face of decreasing antigen concentration, and for ensuring preferential activation of memory T cells upon repeated encounter with antigen.
Falcioni
F
F
Department of Inflammation/Autoimmune Diseases, Hoffmann-La Roche, Inc., Nutley, New Jersey 07110-1199, USA.
Shah
H
H
Vidović
D
D
Morimoto
C
C
Belunis
C
C
Bolin
D
D
Nagy
Z A
ZA
D017951:Antigen Presentation / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D018819:Dipeptidyl Peptidase 4 / Q000276:immunology / Q000502:physiology*; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects; D039222:Integrin alpha1beta1; D019012:Integrin beta1 / Q000276:immunology; D016023:Integrins / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology / Q000502:physiology*; D008565:Membrane Proteins / Q000096:biosynthesis / Q000276:immunology; D010455:Peptides / Q000276:immunology; D011485:Protein Binding / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis; D010566:Virulence Factors, Bordetella / Q000276:immunology
D006684:HLA-DR Antigens; D039222:Integrin alpha1beta1; D019012:Integrin beta1; D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1; D008565:Membrane Proteins; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D010566:Virulence Factors, Bordetella; D018819:Dipeptidyl Peptidase 4