Phenotype and function of CD4+ T cells in mice lacking invariant chain

Area of Science:

• Immunology
• Molecular Biology
• T cell biology

Background:

• The invariant chain (Ii) is crucial for MHC class II molecule assembly, transport, and peptide loading.
• Ii-deficient (Ii zero) mice offer insights into the role of Ii in immune responses.

Purpose of the Study:

• To investigate the impact of altered MHC class II expression in Ii zero mice on CD4+ T cell phenotype and function.
• To determine the role of the thymus in the observed T cell abnormalities.

Main Methods:

• Analysis of T cell populations in the thymus and periphery of Ii zero mice.
• Assessment of T cell activation markers and surface TCR-alpha beta levels.
• Functional assays including responses to mitogens, antibodies, alloantigens, superantigens, and specific antigens.
• Construction and analysis of reciprocal radiation bone marrow chimeras.

Main Results:

• Ii zero mice exhibit a reduced CD4+8- T cell subset.
• Peripheral CD4+ T cells show decreased TCR-alpha beta and express activation markers.
• CD4+ T cells from Ii zero mice have impaired responses to specific antigens and superantigens.
• Chimeric analysis revealed the thymus is responsible for the altered CD4+ T cell phenotype.

Conclusions:

• The absence of Ii in the thymus leads to an altered peptide repertoire presented by MHC class II molecules.
• This altered repertoire significantly impacts CD4+ T cell selection and their subsequent phenotype in the periphery.
• Invariant chain deficiency profoundly affects T cell development and antigen recognition pathways.