A two-step, two-signal model for the primary activation of precursor helper T cells

Peter A. Bretscher*

Department of Microbiology and Immunology, University of Saskatchewan, 107 Wiggins Road, Saskatoon, Saskatchewan, S7N 5E5 Canada

Communicated by David W. Talmage, University of Colorado Health Sciences Center, Denver, CO (received for review June 4, 1998)

Abstract

I present here a new model for the primary activation of precursor helper T cells. Observations demonstrate that the immune system learns not to respond to extrathymic, organ-specific self-antigens because of their early appearance in development. The immune system thus discriminates between peripheral self-antigens and foreign antigens and, when mature, usually makes an immune response against only the latter. Contemporary models for the activation and inactivation of T helper (Th) function do not account for such discrimination. The model proposed here is consistent with contemporary findings and incorporates a mechanism of peripheral self–nonself discrimination.

Footnotes

↵ * To whom reprint requests should be addressed. e-mail: bretschr{at}duke.usask.ca.
ABBREVIATIONS:

Th,

T helper;

pTh,

precursor T helper;

TcR,

T cell receptor;

APC,

antigen-presenting cell;

eTh,

effector T helper;

MHC,

major histocompatibility complex