A structural somatic variant of the Kk antigen is generated by point mutation

Area of Science:

• Immunology
• Molecular Biology
• Genetics

Background:

• The Kk antigen is a crucial Class I molecule involved in T-cell recognition.
• Structural variants of the Kk antigen were previously selected from a T-cell lymphoma.
• These variants were identified by the loss of specific epitopes recognized by monoclonal antibodies.

Purpose of the Study:

• To determine the primary structure of the altered Kk molecules from the HK13.S3 cell line.
• To understand the molecular basis for the altered recognition of the Kk variant by T-cells.

Main Methods:

• Analysis of the primary structure of Kk molecules from the HK13.S3 cell line.
• Comparison of the altered Kk molecule sequence with the parental Kk molecule.

Main Results:

• A single base pair exchange (GCG to GTG) was identified in the Kk molecule from HK13.S3 cells.
• This genetic alteration results in an amino acid substitution: alanine to valine at position 40 of the protein.
• The variant Kk molecule is not recognized by 40% of trinitrophenyl-specific, Kk-restricted cytotoxic T lymphocytes.

Conclusions:

• Minor structural modifications in Class I molecules can profoundly influence H-2 restricted T-cell responses.
• The alanine to valine exchange at position 40 is responsible for the altered T-cell recognition phenotype.
• This study underscores the sensitivity of T-cell receptor interactions to subtle changes in MHC molecule structure.