Responding to the virus Advances in HIV immunology Magalli Magnoumba Africa Health Research Institute CONFLICT OF INTEREST I have no relevant financial relationships with ineligible companies to disclose ID: 1025340
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1. INVESTIGATING THE DEVELOPMENT OF T CELL IMMUNITY IN ACUTE HIV-1 INFECTION THROUGH A LONGITUDINAL ANALYSIS OF THE TCR REPERTOIREResponding to the virus: Advances in HIV immunologyMagalli Magnoumba Africa Health Research Institute
2. CONFLICT OF INTERESTI have no relevant financial relationships with ineligible companies to disclose
3. HARNESSING T-CELL RECEPTORSSource: BiorenderCould we use the same approach for HIV?Which TCRs
4. FRESH STUDYSource: Dong et al., Lancet HIV. 2017 Measuring TCR repertoire in 7 longitudinal samples pre and post HIV infection:Global unbiased examination of total TCR response to Acute HIV infection
5. CONCEPT OF THE STUDYSource: BiorenderPost-infectionPre-infectionExpanded TCRAntigen Presenting cellImmune responseT-cellProliferation of antigen specific T-cellsRepresented in the TCR repertoire as expanded clones
6. DIVERSITY AND CLONAL EXPANSIONClonal expansionDiversityFrequencyNaiveExpanded (>3)Pre-infectionEarly infection (2 – 7 weeks)Mid infection (24 – 36 weeks)Late infection (after 48 weeks)Shannon DiversityControlEarly Mid Late
7. TCR REPERTOIRE OF PARTICIPANT BEFORE AND AFTER HIV INFECTIONVJ Pairing Pre-infectionVJ Pairing Early infectionVJ Pairing Mid infection
8. IDENTIFICATION OF RELATED CLUSTERS WITH EXPANDED TCRJoshi et al., Nat imm. 2019
9. IDENTIFICATION OF RELATED CLUSTERS WITH EXPANDED TCRPre-infection Clusters Early infection ClustersPost-infection clusters
10. CDR3 MOTIFS FROM CLUSTERSCMV MOTIFNovel TCR MOTIFPost-infection clustersTCR Database: VDJdb TCR Logo: ggseqlogo
11. CONCLUSIONTCR repertoire sequencing reveals clear expansions in early HIV infection and can provide an unbiased view of the total HIV-specific T-cell response Bioinformatic approaches can identify clusters of expanded TCR likely to target specific antigens Antigen prediction software can be leveraged to identify important antigenic targets in early HIV that maybe useful in vaccine or TCR engineering strategiesTCR sequencing also provides unbiased view of Donor-Unrestricted T cells (DURTs)
12. ACKNOWLEDGEMENTLeslie LABDr Al LeslieAbigail Tlou NgoepeLerato NdlovuMahlatse MaseemeMark ChambersRobert KlauseFACILITIESKloverpris LabDr Henrik KloverprisLilian FolarinFaiaz AbdoolLivo EsemuNicholas HerbertRAGON INSTITUTEBruce WalkerFUNDINGNdung’u LabProf Thumbi Ndung’uKavidha ReddyNasreen IsmailFRESH TEAMKrista DongAmber MoodleyMary DongFRESH Study TeamFRESH Study Participants