Processing and Presentation of Non-Conventional MHC Ligands (R21 Clinical Trial Not Allowed) | PA 19 066

Opportunity Information: Apply for PA 19 066

The NIH grant opportunity "Processing and Presentation of Non-Conventional MHC Ligands (R21 Clinical Trial Not Allowed)" (Funding Opportunity Number PA-19-066; CFDA 93.855) supports early-stage, exploratory immunology research aimed at understanding how the immune system generates and displays unusual antigens on major histocompatibility complex (MHC) molecules. The central focus is on antigen processing and presentation pathways that produce non-conventional ligands, including both novel peptides and non-peptidic molecules, and how these ligands shape immune recognition. In practical terms, the FOA is looking for studies that can explain where these atypical ligands come from, what cellular machinery produces them, how they are loaded onto MHC molecules, and how immune cells respond to them.

A key goal is to clarify the role these non-standard MHC-presented ligands play in real biological outcomes. That includes whether they contribute to protective immunity against infectious pathogens, whether they influence vaccine-induced immune responses, and whether they drive or limit pathogen-associated immunopathology (immune-mediated tissue damage that occurs during infection). The opportunity also extends to immune-mediated diseases more broadly, encouraging proposals that investigate whether these unique ligands help trigger, worsen, prevent, or slow down immune-driven conditions. The bigger picture is that by identifying and mechanistically explaining these unusual presented antigens, researchers may uncover new immune targets and principles that can be leveraged to design better vaccines, diagnostics, and immune-based therapies.

The mechanism is an R21, which typically emphasizes high-impact, hypothesis-generating, and innovative work rather than large, fully mature programs. The FOA explicitly states "Clinical Trial Not Allowed," meaning applicants should not propose clinical trials or human interventional studies designed to prospectively assign participants to receive an intervention. The work can still be clinically relevant and may involve human samples or observational approaches, as long as it does not cross into a regulated clinical trial design.

From an applicant eligibility standpoint, the FOA is broadly open. Eligible applicants include a wide range of U.S. governmental entities (state, county, city/township, and special district governments), tribal governments (including federally recognized tribal governments and other tribal organizations), public housing authorities/Indian housing authorities, independent school districts, and many categories of higher education institutions (public/state-controlled and private). It also includes nonprofit organizations (both with and without 501(c)(3) status, excluding higher education institutions in those categories), for-profit organizations (other than small businesses), and small businesses. In addition, the announcement highlights other eligible applicants such as Alaska Native and Native Hawaiian Serving Institutions, AANAPISI institutions, Hispanic-serving Institutions, HBCUs, Tribally Controlled Colleges and Universities, faith-based or community-based organizations, eligible federal agencies, U.S. territories or possessions, regional organizations, and non-U.S. entities (foreign organizations), reflecting an intent to encourage broad participation across institution types and geographies.

Administratively, the opportunity is categorized as a discretionary grant in the health research area and is run by the National Institutes of Health. The source data lists an award ceiling of $200,000 and shows the original closing date as 2022-01-07, with a creation date of 2018-11-13. Overall, this FOA is best read as an invitation to pursue innovative, mechanistic studies of underappreciated antigen types and presentation pathways, with the expectation that clarifying these processes will open new directions for vaccines and immunotherapies and improve understanding of protective versus pathogenic immune responses.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Processing and Presentation of Non-Conventional MHC Ligands (R21 Clinical Trial Not Allowed)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.855.
• This funding opportunity was created on 2018-11-13.
• Applicants must submit their applications by 2022-01-07. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Each selected applicant is eligible to receive up to $200,000.00 in funding.
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

Apply for PA 19 066

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