H‐2 Restricted Cytolytic and Noncytolytic T Cell Clones: Isolation, Specificity and Functional Analysis

Helper T cells for cytotoxic T lymphocytes need not be I region restricted

“…We chose to study the H-Y system because it has provided a great deal of the evidence suggesting that helper cells in CTL responses are I region restricted. This evidence relies upon the observation that I region genes influence CTL responses: cells from I b homozygotes but not I k homozygotes make H-Y-specific secondary CTL responses when primed intravenously or intraperitoneally (12)(13)(14)(15). Von Boehmer and Haas (1) demonstrated cellular synergy between cell populations from different radiation chimeras during in vivo priming to H-Y antigen, and their data was consistent with a requirement for Ib-restricted helper T cells for activation of (H-2 b × H-2k)F1 CTL specific for H-Y.…”

“…The absolute requirement of most cloned CTL for exogenous IL-2 (15,20,33) that is produced by T cells (34)(35)(36) argues that a discrete helper T cell is required and that at least one function of this cell is to provide IL-2 as well as possibly other soluble mediators to CTL.…”

“…We conclude that the recognition of antigen by receptors on m a t u r e C T L is involved in the growth of these C T L lines. This property thus distinguishes these C T L lines from C T L lines that grow continuously in Sp Con ASn alone (15) and those that require syngeneic filler cells plus Sp Con ASn (38).…”

“…Experiments interpreted as supporting the role of I region-recognition events during the process of CTL induction include (a) studies demonstrating the augmentation of CTL responses to foreign H-2K and D antigens by I region-reactive T cells (5,6), (b) studies of CTL responses to viral (2) or non-H-2 cell surface antigens (7) or hapten (8), demonstrating an influence of I region genes expressed by cells of the thymus on the response phenotype of T cells that mature therein, (c) a study demonstrating the apparent depletion, by in vivo negative selection procedures, of I region-restricted helper cells required for an in vitro secondary CTL response specific for minor histocompatibility antigens (9), and (d) the finding that Ia + non-T accessory cells are required for in vitro CTL responses (4, 10, 1 1). In addition, studies of the Ir gene defect ofnonresponder strains in the CTL response of female mice to the male antigen, H-Y, have been interpreted in terms of I region-restricted helper T cells (1,7,(12)(13)(14)(15).…”

Genetic linkage of the cytolytic T lymphocyte repertoire and immunoglobulin heavy chain genes.

“…Evidence that anti-idiotypic antibodies prepared against immunoglobulin bind T cells or T cell products that demonstrate the appropriate antigen specificity suggests genetic linkage between T and B cell idiotypes (1-5). In contrast, T lymphocytes that demonstrate a requirement for recognition of molecules encoded by the major histocompatibility complex (MHC) as well as foreign antigen, such as proliferative or cytolytic T lymphocytes (CTL), do not appear to express idiotypes that predominate in antibody responses (4,(6)(7)(8)). An alternative strategy that has been successfully applied to the study of genetic control of allospecific T cell receptors has been to obtain anti-idiotypic antisera by direct immunization with allospecific T cells (2, 4).…”