Minimal requirements for peptide mediated activation of CD8+ CTL.
A physical chemical model of T cell stimulation by class I-peptide complexes was developed and used to analyse in vitro studies of gamma-interferon release as a function of the number of peptide and MHC molecules. The analysis provided reasonable estimates of well identified parameters, including equilibrium constants and the minimum number of T cell receptor-class I-peptide ternary complexes on a presenting cell required to activate T cells. The latter number was estimated as 3-5 per T cell. This is in distinct contrast to estimates in the literature of the number of peptide-MHC complexes required for activity, which is necessarily larger. The analysis also predicted that activity is potentiated by interaction between class I molecules, even if one member of the pair is not bound by antigen. The analytical approach used in this paper may be applicable to other activation systems.
Department of Electrical, Computer and Systems Engineering, Boston University, MA 02215.
R C
RC
Brower
R
R
England
T
T
Takeshita
S
S
Kozlowski
D H
DH
Margulies
J A
JA
Berzofsky
C
C
Delisi
D016475:3T3 Cells; D000494:Allosteric Regulation; D000595:Amino Acid Sequence; D000818:Animals; D015686:Gene Products, env / Q000276:immunology; D006183:H-2 Antigens / Q000276:immunology; D019302:HIV Envelope Protein gp160; D064532:Histocompatibility Antigen H-2D; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D008285:Major Histocompatibility Complex / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018448:Models, Immunological; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology*; D011498:Protein Precursors / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D015686:Gene Products, env; D006183:H-2 Antigens; D019302:HIV Envelope Protein gp160; D064532:Histocompatibility Antigen H-2D; D010455:Peptides; D011498:Protein Precursors; D007371:Interferon-gamma