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Investigating the Immune Response to Mycobacterium Tuberculosis Complex (MTBC) Variable Antigens
Investigating the Immune Response to Mycobacterium Tuberculosis Complex (MTBC) Variable Antigens
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20260202103114
- ISBN
- 9798280752948
- DDC
- 616.079
- 저자명
- Howard, Zach.
- 서명/저자
- Investigating the Immune Response to Mycobacterium Tuberculosis Complex (MTBC) Variable Antigens
- 발행사항
- [Sl] : University of California, San Francisco, 2025
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2025
- 형태사항
- 76 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 86-12, Section: B.
- 주기사항
- Advisor: Ernst, Joel;Javid, Babak.
- 학위논문주기
- Thesis (Ph.D.)--University of California, San Francisco, 2025.
- 초록/해제
- 요약Mycobacterium tuberculosis is the leading cause of death globally due to a single infectious agent. Currently, no effective vaccine against pulmonary tuberculosis, the primary adult disease caused by Mtb infection, exists. A large body of evidence suggests that CD4 T cell responses to Mtb infection are required to prevent disease, and thus most current vaccine studies aim to induce protective CD4 T cell responses. Unlike viral pathogens or bacteria that produce a toxin, Mtb has an exceptionally large number of suitable CD4 T cell antigens and ideal targets for inclusion in a vaccine have not been exhaustively identified. Intriguingly, efforts to identify signs of antigenic variation within the Mycobacterium tuberculosis complex revealed that T cell antigens are hyperconserved. This suggests that most dominant T cell epitopes are not inducing immune responses that exert a selective pressure on Mtb during infection and may not be suitable for a vaccine. Additional studies identified a rare subset of antigens that did exhibit sequence variation within predicted T cell epitopes. I hypothesized that T cell responses to these antigens may be more protective. Utilizing a DNA vaccine platform and aerosol infection of multiple strains of mice, I was able to demonstrate that a vaccination with these antigens induced a CD4 T cell response and altered pathology in two strains of mice, independent of bacterial burden. I further demonstrated significant changes to the immune cell subsets responding to infection and to the characteristic granulomatous lesion mediated by variable antigen vaccination. Additionally, I showed that vaccination with these antigens significantly changed the immune cell composition in the lungs during infection. Lastly, I established novel experimental methods that will aid in investigating the mechanisms underlying these unique impacts of CD4 T cell responses to variable Mtb antigens.
- 일반주제명
- Immunology
- 일반주제명
- Microbiology
- 일반주제명
- Public health
- 키워드
- Immune pathology
- 키워드
- Mouse models
- 키워드
- T cells
- 키워드
- Vaccines
- 기타저자
- University of California, San Francisco Biomedical Sciences
- 기본자료저록
- Dissertations Abstracts International. 86-12B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■006m o d
■007cr#unu||||||||
■020 ▼a9798280752948
■035 ▼a(MiAaPQ)AAI31936822
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a616.079
■1001 ▼aHoward, Zach.▼0(orcid)0000-0002-1958-4638
■24510▼aInvestigating the Immune Response to Mycobacterium Tuberculosis Complex (MTBC) Variable Antigens
■260 ▼a[Sl]▼bUniversity of California, San Francisco▼c2025
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2025
■300 ▼a76 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 86-12, Section: B.
■500 ▼aAdvisor: Ernst, Joel;Javid, Babak.
■5021 ▼aThesis (Ph.D.)--University of California, San Francisco, 2025.
■520 ▼aMycobacterium tuberculosis is the leading cause of death globally due to a single infectious agent. Currently, no effective vaccine against pulmonary tuberculosis, the primary adult disease caused by Mtb infection, exists. A large body of evidence suggests that CD4 T cell responses to Mtb infection are required to prevent disease, and thus most current vaccine studies aim to induce protective CD4 T cell responses. Unlike viral pathogens or bacteria that produce a toxin, Mtb has an exceptionally large number of suitable CD4 T cell antigens and ideal targets for inclusion in a vaccine have not been exhaustively identified. Intriguingly, efforts to identify signs of antigenic variation within the Mycobacterium tuberculosis complex revealed that T cell antigens are hyperconserved. This suggests that most dominant T cell epitopes are not inducing immune responses that exert a selective pressure on Mtb during infection and may not be suitable for a vaccine. Additional studies identified a rare subset of antigens that did exhibit sequence variation within predicted T cell epitopes. I hypothesized that T cell responses to these antigens may be more protective. Utilizing a DNA vaccine platform and aerosol infection of multiple strains of mice, I was able to demonstrate that a vaccination with these antigens induced a CD4 T cell response and altered pathology in two strains of mice, independent of bacterial burden. I further demonstrated significant changes to the immune cell subsets responding to infection and to the characteristic granulomatous lesion mediated by variable antigen vaccination. Additionally, I showed that vaccination with these antigens significantly changed the immune cell composition in the lungs during infection. Lastly, I established novel experimental methods that will aid in investigating the mechanisms underlying these unique impacts of CD4 T cell responses to variable Mtb antigens.
■590 ▼aSchool code: 0034.
■650 4▼aImmunology
■650 4▼aMicrobiology
■650 4▼aPublic health
■653 ▼aAntigenic variation
■653 ▼aImmune pathology
■653 ▼aMouse models
■653 ▼aMycobacterium tuberculosis
■653 ▼aT cells
■653 ▼aVaccines
■690 ▼a0982
■690 ▼a0410
■690 ▼a0573
■71020▼aUniversity of California, San Francisco▼bBiomedical Sciences.
■7730 ▼tDissertations Abstracts International▼g86-12B.
■790 ▼a0034
■791 ▼aPh.D.
■792 ▼a2025
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17357001▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
