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.Apply for PA 19 066
- 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.
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FAQs: NIH PA-19-066 - Processing and Presentation of Non-Conventional MHC Ligands (R21 Clinical Trial Not Allowed)
What is this NIH funding opportunity?
This opportunity is the NIH Funding Opportunity Announcement (FOA) titled "Processing and Presentation of Non-Conventional MHC Ligands (R21 Clinical Trial Not Allowed)" with Funding Opportunity Number PA-19-066 and CFDA 93.855. It supports early-stage, exploratory immunology research focused on how the immune system generates and presents unusual antigens on major histocompatibility complex (MHC) molecules.
What is the main scientific focus of the FOA?
The FOA centers on antigen processing and presentation pathways that generate non-conventional ligands for MHC molecules. This includes both novel peptides and non-peptidic molecules, and how these ligands influence immune recognition and immune responses.
What does "non-conventional MHC ligands" mean in the context of this opportunity?
Within the scope described, non-conventional MHC ligands refers to atypical antigens displayed by MHC molecules, including novel peptide ligands and non-peptidic molecules. The emphasis is on understanding where these ligands come from and the cellular processes that produce and load them onto MHC.
What kinds of research questions is NIH looking for under this FOA?
The FOA is looking for mechanistic studies that explain: (1) the origin of atypical MHC-presented ligands, (2) what cellular machinery and pathways generate them, (3) how they are loaded onto MHC molecules, and (4) how immune cells respond to them.
Does the FOA emphasize mechanism, discovery, or application?
Based on the description provided, the emphasis is strongly mechanistic and discovery-oriented (how non-conventional ligands are produced and presented, and how they shape immune recognition). At the same time, it also encourages connecting those mechanisms to real biological outcomes, such as protective immunity, vaccine responses, and immunopathology.
How does this FOA relate to infectious diseases and vaccines?
The FOA explicitly highlights interest in whether non-standard MHC-presented ligands contribute to protective immunity against infectious pathogens, influence vaccine-induced immune responses, and drive or limit pathogen-associated immunopathology (immune-mediated tissue damage during infection).
Is immune-mediated disease research within scope?
Yes. The opportunity encourages proposals that investigate whether these unique MHC-presented ligands help trigger, worsen, prevent, or slow down immune-driven conditions more broadly, beyond infection-specific contexts.
What is the broader impact NIH is aiming for?
The bigger-picture goal described is that identifying and explaining unusual MHC-presented antigens may reveal new immune targets and guiding principles that could be leveraged for better vaccines, diagnostics, and immune-based therapies.
What type of grant mechanism is this?
This FOA uses the NIH R21 mechanism. R21 awards generally support early-stage, exploratory, and potentially high-impact work that is hypothesis-generating and innovative, rather than large, fully developed research programs.
Are clinical trials allowed under this opportunity?
No. The FOA explicitly states "Clinical Trial Not Allowed," which means applicants should not propose a clinical trial or a human interventional study that prospectively assigns participants to receive an intervention.
Can the research still use human samples or be clinically relevant?
Yes. The description indicates the work can be clinically relevant and may involve human samples or observational approaches, as long as it does not cross into a clinical trial design where participants are prospectively assigned to an intervention.
Who is eligible to apply?
Eligibility is broad. Eligible applicants include many U.S. governmental entities (state, county, city/township, and special district governments), tribal governments (federally recognized and other tribal organizations), public housing authorities/Indian housing authorities, independent school districts, and a wide range of higher education institutions (public/state-controlled and private). The FOA also includes nonprofits (with and without 501(c)(3) status, excluding higher education institutions in those nonprofit categories), for-profit organizations (other than small businesses), small businesses, and additional categories highlighted in the announcement.
Are minority-serving and community-based institutions encouraged or included?
Yes. The opportunity explicitly highlights eligibility for Alaska Native and Native Hawaiian Serving Institutions, AANAPISI institutions, Hispanic-serving Institutions, HBCUs, Tribally Controlled Colleges and Universities, as well as faith-based or community-based organizations.
Can federal agencies apply?
Yes. The eligibility list includes eligible federal agencies.
Are applicants outside the United States eligible?
Yes. The eligibility information provided indicates non-U.S. entities (foreign organizations) are included, and it also references U.S. territories or possessions and regional organizations.
What is the award ceiling listed for this opportunity?
The source data provided lists an award ceiling of $200,000.
What is the program area and administering agency?
This is a discretionary grant in the health research area, administered by the National Institutes of Health (NIH).
What is the Funding Opportunity Number (FON) and CFDA number?
The Funding Opportunity Number is PA-19-066, and the CFDA number listed is 93.855.
What was the closing date listed in the source information?
The original closing date shown in the source information is 2022-01-07.
When was this opportunity created, based on the provided data?
The creation date listed in the source information is 2018-11-13.
What types of outcomes or endpoints are emphasized in the FOA description?
The description emphasizes biological outcomes related to immunity, including protective immune responses to pathogens, vaccine-induced immunity, and pathogen-associated immunopathology. It also emphasizes outcomes in immune-mediated diseases, including roles in triggering, worsening, preventing, or slowing immune-driven conditions.
What makes a project a good fit for an R21 in this topic area?
Based on the description provided, a good fit would be innovative, exploratory, hypothesis-generating research that digs into underappreciated antigen types and presentation pathways, with a clear mechanistic angle and a rationale for how clarifying these processes could open new directions for vaccines, diagnostics, or immune-based therapies.
Does the FOA limit projects to peptide antigens only?
No. The description specifically includes both novel peptides and non-peptidic molecules as non-conventional ligands of interest.
Is the FOA focused only on MHC loading, or does it include upstream and downstream biology?
It includes the full chain described: where atypical ligands originate, what cellular machinery generates them, how they are loaded onto MHC molecules, and how immune cells respond to those presented ligands.
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