A key question in CD1 biology that is relevant to its translational potential is how CD1-specific T cells respond during natural infection in humans. Two extreme possibilities are: 1) CD1a, CD1b, and CD1c-specific T cells expand from a naive, low precursor frequency population and acquire memory function and phenotype during infection, just like MHC-restricted T cells, or 2) CD1a, CD1b, and CD1c-specific T cells behave like CD1d-specific NKT cells and have a constitutively activated phenotype that does not change during infection, as well as an unchanged frequency.

To address this question, we use CD1 tetramers loaded with synthetic versions of lipid antigens that are present in Mycobacterium tuberculosis bacteria. We use seven different tetramers to study T cells in a patient cohort from Lima, Peru, consisting of 50 active tuberculosis cases, 50 uninfected household contacts, and 50 infected, but non-progressing household contacts. These experiments establish immunodominance among the used lipid antigens and frequency of tetramer-positive T cell populations.

Another question in the CD1a, CD1b, and CD1c field is whether the T cell repertoire of the responding human T cells is predictable and interpretable. This question is addressed by high throughput sequencing of tetramer-positive T cell populations. Together, our datasets help answer the question whether CD1-presented lipid antigens can be of use in vaccination and diagnostics.