We are defining the molecular and cellular mechanisms which control the age-associated changes in immune response and the functional role played by MHC molecules in tumor escape from immune surveillance. During differentiation in the thymus, T cells bearing self-reactive TCRs are deleted. We are studying the appearance of these T cells later in life. Only T cells which recognize antigen in association with self-MHC molecules are positively selected within the thymus. We are investigating MHC-restricted helper T cell function for specific antibody production in young, adult and old mice.
Influenza remains a major cause of morbidity and mortality amongst the elderly.
We plan to identify the proportion of subjects who do not respond to influenza vaccination and to determine the mechanisms which control the response to vaccination. We are examining the levels of sHLA-I molecules in the serum of elderly subjects vaccinated against influenza virus. We have found that malignant transformation is frequently associated with a marked loss of polymorphic MHC class I molecules. The selective loss of an HLA class I polymorphic epitope, by which tumor cells may escape CTL recognition and NK surveillance is being studied. Predictive value of IgD-receptor upregulation on peripheral blood T cells for the antibody response to influenza vaccination in the elderly.