# HLA Alleles and the Progression of Human Cryptococcosis

> **NIH NIH R21** · UNIVERSITY OF MINNESOTA · 2020 · $244,611

## Abstract

Project Summary
Cryptococcus continues to cause significant disease in immunocompromised individuals, particularly
those with HIV/AIDS. Understanding the interplay between the human immune system and this
pathogenic fungus is critical if we hope to improve clinical outcomes. The overall scientific objective of
the research is to understand how the immune system in humans is directed towards a protective or
deleterious response in Cryptococcus infection, while the specific objective of this proposal is to
determine factors that impact the helper T cell response in humans during cryptococcal meningitis.
Notably, there is particular interest in how the HLA/MHC system influences CD4+ T cells in their
response to Cryptococcus. To accomplish this, the first aim is to identify the most prevalent HLA
alleles in persons with cryptococcal disease. The hypothesis is that certain HLA alleles are
associated with developing progressive disease, while others are associated with attenuating or
protecting against disease. Establishing HLA-disease associations not only carries important clinical
and therapeutic implications, but creates the knowledge base for further immunological studies. Aim
two will use immunophenotyping modalities to determine helper T cell responses in the cryptococcal-
specific immune response. The use of CD4+ T cell tetramers on cells from HIV-infected humans
provides a proof-of-concept model for the study of infectious disease-specific T cell responses going
forward. Additionally, performing activation induced marker (AIM) assays on the same cohort will
provide a comparator method in the testing of the hypothesis that Th1 helper T responses are more
protective in cryptococcosis than Th2 responses. The data generated by this study will drive
innovation in the areas of vaccine development, personalized medicine, and health systems
implementation. By establishing the necessary data on HLA prevalence of our study population and
successfully implementing our proposed immunology methods to determine disease-specific T cell
responses, we will lay the foundation for future clinical and basic science studies to understand how
the human immune system responds to infection with Cryptococcus and manipulate that response to
reduce disease.

## Key facts

- **NIH application ID:** 10049083
- **Project number:** 1R21AI150303-01A1
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Kirsten Nielsen
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $244,611
- **Award type:** 1
- **Project period:** 2020-06-15 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10049083

## Citation

> US National Institutes of Health, RePORTER application 10049083, HLA Alleles and the Progression of Human Cryptococcosis (1R21AI150303-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10049083. Licensed CC0.

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