High-avidity CTL exploit two complementary mechanisms to provide better protection against viral infection than low-avidity CTL.
Previously, we observed that high-avidity CTL are much more effective in vivo than low-avidity CTL in elimination of infected cells, but the mechanisms behind their superior activity remained unclear. In this study, we identify two complementary mechanisms: 1) high-avidity CTL lyse infected cells earlier in the course of a viral infection by recognizing lower Ag densities than those distinguished by low-avidity CTL and 2) they initiate lysis of target cells more rapidly at any given Ag density. Alternative mechanisms were excluded, including: 1) the possibility that low-avidity CTL might control virus given more time (virus levels remained as high at 6 days following transfer as at 3 days) and 2) that differences in efficacy might be correlated with homing ability. Furthermore, adoptive transfer of high- and low-avidity CTL into SCID mice demonstrated that transfer of a 10-fold greater amount of low-avidity CTL could only partially compensate for their decreased ability to eliminate infected cells. Thus, we conclude that high-avidity CTL exploit two complementary mechanisms that combine to prevent the spread of virus within the animal: earlier recognition of infected cells when little viral protein has been made and more rapid lysis of infected cells.
Derby
M
M
Molecular Immunogenetics and Vaccine Research Section, Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1578, USA.
Alexander-Miller
M
M
Tse
R
R
Berzofsky
J
J
D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation; D002460:Cell Line; D002465:Cell Movement / Q000276:immunology; D002999:Clone Cells; D003601:Cytotoxicity Tests, Immunologic / Q000379:methods; D003602:Cytotoxicity, Immunologic; D005260:Female; D015488:HIV Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D019302:HIV Envelope Protein gp160 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D016513:Mice, SCID; D010049:Ovarian Diseases / Q000276:immunology / Q000821:virology; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation / Q000821:virology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation / Q000821:virology*; D014407:Tumor Cells, Cultured; D014615:Vaccinia / Q000276:immunology / Q000821:virology; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology; D019562:Viral Load
D015488:HIV Antigens; D019302:HIV Envelope Protein gp160; C087213:HIV-1 gp160 (315-329); D010446:Peptide Fragments