Genetic analysis of the presentation of minor lymphocyte-stimulating determinants. II. Differing non-MHC control of super-stimulatory and more poorly stimulatory Mls phenotypes.
Analysis of the capacity of splenocytes from non-prototypic Mlsa or Mlsc mouse strains to stimulate allogeneic H-2k-compatible T cells in a primary Mls-defined MLR provided interesting examples of exceptions to the usually stated characterization of Mlsa and Mlsc determinants as highly stimulatory of weakly stimulatory, respectively. Across the Mlsa barrier, MA/My stimulator cells had a significantly reduced capacity to elicit responder proliferation in comparison with prototypic AKR/J or less well studied C58/J, CE/J, or RF/J splenocytes. Across the Mlsc barrier, a gradient of stimulatory ability was observed with RF/J splenocytes being virtually nonstimulatory, prototypic C3H/HeJ splenocytes having an intermediate capacity, and CE/J and C58/J being highly stimulatory presenters of this non-MHC specificity. The differing capacity of each of these H-2k stimulator cells to elicit unprimed responder cell proliferation across an Mlsa or Mlsc difference correlated with the T cell growth factor activity that was secreted into the MLR supernatants. The super stimulatory form of Mlsc was expressed in an autosomal dominant fashion by (Mlsc poorly stimulatory x Mlsc super-stimulatory)F1 animals, (BALB.K x C58/J)F1 or (RF/J x CE/J)F1. The segregation of Mlsc stimulatory ability among first backcross and F2 animals derived from the former F1 was compatible with a single non-MHC gene controlling the expression and presentation of the super-stimulatory form of Mlsc. The regulatory nature of this gene was indicated by the observation that F1 animals generated from the Mlsc nonprototypic and poorly stimulatory BALB/c parental strain were self-tolerant to the super-stimulatory form of Mlsc. The existence of an Mls specificity other than a and c was suggested by positive non-MHC MLR responses in certain responder/stimulator cell combinations of Mls prototypic and nonprototypic mouse strains.
Ryan
J J
JJ
Immunobiology and Transplantation Department, Naval Medical Research Institute, Bethesda, MD 20814-5055.
LeJeune
H B
HB
Mond
J J
JJ
Finkelman
F D
FD
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D005802:Genes, MHC Class II; D007108:Immune Tolerance; D007153:Immunologic Deficiency Syndromes / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D016747:Minor Lymphocyte Stimulatory Antigens; D013154:Spleen / Q000276:immunology
D000954:Antigens, Surface; D007376:Interleukin-2; D016747:Minor Lymphocyte Stimulatory Antigens; D015847:Interleukin-4