Metabolically active antigen presenting cells are required for human T cell proliferation in response to the

M A Tomai1, E H Beachey, G Majumdar

  • 1VA Medical Center, Memphis, TN 38104.

Insights

Streptococcal M protein acts as a superantigen, activating T cells. It requires accessory cells with MHC class II but not processing for T cell activation, suggesting direct complex formation.

Area of Science:

  • Immunology
  • Microbial Pathogenesis

Background:

  • Group A Streptococcus M protein is a superantigen activating T cells expressing specific V beta elements of the T cell receptor (TCR).
  • Understanding the molecular and cellular presentation requirements for M protein superantigens is crucial for elucidating T cell activation pathways.

Purpose of the Study:

  • To investigate the molecular and cellular requirements for the presentation of M protein (pep M5) to T cells.
  • To determine the role of accessory cells (AC) and antigen-presenting cells (APC) in T cell activation by pep M5.

Main Methods:

  • Utilized a 22 kDa fragment of M protein (pep M5) to study T cell activation.
  • Investigated the necessity of accessory cells expressing MHC class II molecules.
  • Examined the role of antigen processing by APCs.
  • Assessed the impact of paraformaldehyde (PF) fixation on APCs and T cell proliferation.
  • Evaluated the effect of adding recombinant interleukin-1 (rIL-1) and IL-6.

Main Results:

  • Accessory cells expressing MHC class II molecules were essential for T cell activation by pep M5.
  • Antigen processing by APCs was not required for T cell proliferation induced by pep M5.
  • PF-fixed APCs showed impaired T cell proliferation but maintained IL-2 production; this was restored by rIL-1 and IL-6.
  • PF-fixation of Raji B lymphoma cells did not impede pep M5 presentation to human T cells.

Conclusions:

  • Pep M5 directly associates with HLA class II molecules, forming a complex that induces IL-2 production.
  • Optimal T cell proliferation requires additional signals from accessory cells beyond the M protein-HLA class II complex.

Related Concept Videos

Cell-mediated Immune Responses01:40

Cell-mediated Immune Responses

Overview
Antigens Involved in Adaptive Immunity01:26

Antigens Involved in Adaptive Immunity

An antigen is any substance the immune system identifies as foreign and potentially harmful to the body, prompting an immune response. Antigens have two functional properties: immunogenicity and reactivity. Immunogenicity is the ability of an antigen to stimulate a specific immune response. At the same time, reactivity describes the antigen's ability to react with the cells and antibodies produced in response to it.
Complete Antigens
Complete antigens possess both immunogenicity and reactivity.
Antigen Presenting Cells01:22

Antigen Presenting Cells

The immune system is a complex network of cells and molecules that protects the body from foreign invaders. T cells, a type of white blood cell, play a crucial role in this process. They recognize and attack foreign substances, such as pathogens, that enter the body.
T cells require the help of antigen-presenting cells (APCs), which process foreign antigens into smaller fragments that can be recognized by T cells. These APCs are highly specialized cells that efficiently internalize antigens...
Antigen Processing Pathways01:31

Antigen Processing Pathways

MHC molecules are key players in the immune response, enabling T cells to recognize and respond to specific antigens. They are present on the surface of all nucleated cells in the body and are instrumental in presenting antigens to T cells and activating them. T cells recognize the MHC-antigen complex and initiate an immune response. MHC class I and MHC class II are two main types of MHC molecules, each associated with a distinct antigen processing pathway.
MHC Class I: Presenting Endogenous...
T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
B Cell Activation and Differentiation01:24

B Cell Activation and Differentiation

The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...