Recognition of idiotypic structures in the thymus

Area of Science:

• Immunology
• Developmental Biology
• T-cell Biology

Background:

• T cells undergo selection in the thymus to recognize self-MHC antigens.
• The development of T cells recognizing altered self-antigens is debated, with questions about intrathymic vs. peripheral shaping and the role of internal vs. external factors.

Purpose of the Study:

• To investigate whether the T-cell repertoire for recognizing altered self is shaped intrathymically or peripherally.
• To determine if this repertoire is shaped exclusively by external antigens or influenced by the internal environment.

Main Methods:

• Analysis of thymocyte and spleen cell responsiveness during post-natal development.
• In vitro cultures of thymocytes stimulated with nominal antigen (trinitrophenyl-ovalbumin) and an anti-TNP monoclonal antibody (Sp6).
• In vivo stimulation with TNP conjugates and detection of antigen-specific clones.

Main Results:

• Early in life, thymocytes proliferated in response to Sp6 (recognizing processed immunoglobulin) but not nominal antigen.
• In vivo TNP stimulation increased Sp6-reactive thymocyte clones.
• Thymocyte proliferative capacity decreased with age.
• Spleen cell responses showed age-dependent increases in antigen-specific clones but decreased Sp6 responses.

Conclusions:

• The T-cell repertoire appears to be shaped during intrathymic development.
• This shaping is influenced by the B-cell repertoire and further modulated by external antigens.