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.
Brower
R C
RC
Department of Electrical, Computer and Systems Engineering, Boston University, MA 02215.
England
R
R
Takeshita
T
T
Kozlowski
S
S
Margulies
D H
DH
Berzofsky
J A
JA
Delisi
C
C
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