Carolien van de Sandt
@cvandesandt.bsky.social
Team leader Murdoch Children’s Research Institute (MCRI) and Honorary Senior Research Fellow at the University of Melbourne | Immunology | Virology | Influenza | COVID19 | Aging | T cells | TCRs
I'm deeply honoured & grateful to have been awarded the #CSLCentenaryFellowship at the #AAHMS dinner last week
Many thanks to my mentors & colleagues for their support
Congratulations to my Fellow winner @rhyswg.bsky.social
#MedicalResearch
#CSLCentenaryFellowships
#WomenInSTEMM
@mcri.bsky.social
Many thanks to my mentors & colleagues for their support
Congratulations to my Fellow winner @rhyswg.bsky.social
#MedicalResearch
#CSLCentenaryFellowships
#WomenInSTEMM
@mcri.bsky.social
November 7, 2025 at 7:50 AM
I'm deeply honoured & grateful to have been awarded the #CSLCentenaryFellowship at the #AAHMS dinner last week
Many thanks to my mentors & colleagues for their support
Congratulations to my Fellow winner @rhyswg.bsky.social
#MedicalResearch
#CSLCentenaryFellowships
#WomenInSTEMM
@mcri.bsky.social
Many thanks to my mentors & colleagues for their support
Congratulations to my Fellow winner @rhyswg.bsky.social
#MedicalResearch
#CSLCentenaryFellowships
#WomenInSTEMM
@mcri.bsky.social
We demonstrated that the lower probability of generation of older TCRb chains underpins the decrease in TCR similarity within the A2M1-specific TCRab repertoire of older adults over time.
April 24, 2025 at 10:58 AM
We demonstrated that the lower probability of generation of older TCRb chains underpins the decrease in TCR similarity within the A2M1-specific TCRab repertoire of older adults over time.
Decline in adults public TCRs is compensated by expansion of similar TCRs which express public CDR3 motifs with strong avidity for A2M1. Older TCR repertoires lack public-CDR3 motifs, resulting in expansion of low similar TCRs with private CDR3 motifs & lower avidity for A2M1.
April 24, 2025 at 10:58 AM
Decline in adults public TCRs is compensated by expansion of similar TCRs which express public CDR3 motifs with strong avidity for A2M1. Older TCR repertoires lack public-CDR3 motifs, resulting in expansion of low similar TCRs with private CDR3 motifs & lower avidity for A2M1.
Young public clonotypes (associated with higher functionality) and older private clonotypes (associated with lower functionality) are long-lived and can be detected over the course of 12 years but gradually decline over time.
April 24, 2025 at 10:58 AM
Young public clonotypes (associated with higher functionality) and older private clonotypes (associated with lower functionality) are long-lived and can be detected over the course of 12 years but gradually decline over time.
Adult TCR repertoires were relative stable across timepoints, the limited diversity resulted from broader TCRa gene usage. Heterogenic changes were observed in older TCR repertoires across timepoints, both the TCRa & TCRb chain contribute to diversifying older TCR repertoires.
April 24, 2025 at 10:58 AM
Adult TCR repertoires were relative stable across timepoints, the limited diversity resulted from broader TCRa gene usage. Heterogenic changes were observed in older TCR repertoires across timepoints, both the TCRa & TCRb chain contribute to diversifying older TCR repertoires.
Your immune system gradually loses it top team players when we get older 👱➡️👵
Our study in @ebiomedicine.bsky.social investigates how long good immune cells stay around – a 🧵⬇️ go.unimelb.edu.au/4sep
@katherinekedz.bsky.social @thedohertyinst.bsky.social #Influenza #AgingResearch #Immunity #TCR
Our study in @ebiomedicine.bsky.social investigates how long good immune cells stay around – a 🧵⬇️ go.unimelb.edu.au/4sep
@katherinekedz.bsky.social @thedohertyinst.bsky.social #Influenza #AgingResearch #Immunity #TCR
April 24, 2025 at 10:58 AM
Your immune system gradually loses it top team players when we get older 👱➡️👵
Our study in @ebiomedicine.bsky.social investigates how long good immune cells stay around – a 🧵⬇️ go.unimelb.edu.au/4sep
@katherinekedz.bsky.social @thedohertyinst.bsky.social #Influenza #AgingResearch #Immunity #TCR
Our study in @ebiomedicine.bsky.social investigates how long good immune cells stay around – a 🧵⬇️ go.unimelb.edu.au/4sep
@katherinekedz.bsky.social @thedohertyinst.bsky.social #Influenza #AgingResearch #Immunity #TCR
Despite a smaller total CD8 Tnaïve population in older CMV- & CMV+ individuals, our study found a broad & robust SARS-CoV-2-specific memory CD8 T cell response in both younger & older convalescent COVID-19 donors regardless of CMV status. This was maintained at an epitope level
March 13, 2025 at 11:54 PM
Despite a smaller total CD8 Tnaïve population in older CMV- & CMV+ individuals, our study found a broad & robust SARS-CoV-2-specific memory CD8 T cell response in both younger & older convalescent COVID-19 donors regardless of CMV status. This was maintained at an epitope level
Heterotetramer combinatorial coding allowed simultaneous screening of up to 26 epitopes simultaneously within a single individual directly ex vivo. SARS-CoV-2-specfic CD8 T cells were identified as double-positive for two fluorophores
March 13, 2025 at 11:54 PM
Heterotetramer combinatorial coding allowed simultaneous screening of up to 26 epitopes simultaneously within a single individual directly ex vivo. SARS-CoV-2-specfic CD8 T cells were identified as double-positive for two fluorophores
We observed no differences in total CD8 T cell frequency when comparing all groups. However, younger CMV+ & older individuals had significantly smaller total naïve T cell populations & older CMV+ individuals had a larger terminally differentiated CD8 T cell population
March 13, 2025 at 11:54 PM
We observed no differences in total CD8 T cell frequency when comparing all groups. However, younger CMV+ & older individuals had significantly smaller total naïve T cell populations & older CMV+ individuals had a larger terminally differentiated CD8 T cell population
We studied SARS-CoV-2-specicific CD8 T cells in HLA class I-matched convalescent patients expressing one or more of 10 high-prevalent HLA allotypes. Overall, our study included 35 SARS-CoV-2 epitope-specific CD8 T cell populations across 5 proteins.
March 13, 2025 at 11:54 PM
We studied SARS-CoV-2-specicific CD8 T cells in HLA class I-matched convalescent patients expressing one or more of 10 high-prevalent HLA allotypes. Overall, our study included 35 SARS-CoV-2 epitope-specific CD8 T cell populations across 5 proteins.
The #COVID19 pandemic represented a unique opportunity to study immune responses to a novel pathogen. We compared the SARS-CoV-2-specific CD8 T cell response of younger and older individuals stratified by CMV status who were infected during the first wave of the pandemic.
March 13, 2025 at 11:54 PM
The #COVID19 pandemic represented a unique opportunity to study immune responses to a novel pathogen. We compared the SARS-CoV-2-specific CD8 T cell response of younger and older individuals stratified by CMV status who were infected during the first wave of the pandemic.
Do age & CMV affect the generation of T cell responses against novel pathogens? 🧑🔬 Our @eurjimmunol.bsky.social study shows broad & robust memory #SARS-CoV-2 specific T cell response regardless of age or CMV #Ageingresearch.🧵⬇️ go.unimelb.edu.au/w76p @jetvddijssel.bsky.social @Sanquin @TheDohertyInst
March 13, 2025 at 11:54 PM
Do age & CMV affect the generation of T cell responses against novel pathogens? 🧑🔬 Our @eurjimmunol.bsky.social study shows broad & robust memory #SARS-CoV-2 specific T cell response regardless of age or CMV #Ageingresearch.🧵⬇️ go.unimelb.edu.au/w76p @jetvddijssel.bsky.social @Sanquin @TheDohertyInst
Age-specific TCRs display reduced ability to recognise peptide variants. Older private TCRs displayed unique A2M1 binding profiles, underpinning their reduced binding capacity, avidity, functionality and proliferating capacity compared to other prominent age-specific TCRs
November 30, 2024 at 11:10 AM
Age-specific TCRs display reduced ability to recognise peptide variants. Older private TCRs displayed unique A2M1 binding profiles, underpinning their reduced binding capacity, avidity, functionality and proliferating capacity compared to other prominent age-specific TCRs
A2M1-specific TCRs from older adults had reduced activation capacity compared to public and other age-specific TCRs
November 30, 2024 at 11:10 AM
A2M1-specific TCRs from older adults had reduced activation capacity compared to public and other age-specific TCRs
Older TCRs had a lower binding avidity. The CD8 co-receptors enhanced binding avidity of age-specific private TCRs representing newborn, child, one adult and one older TCR, but had less impact on weak-binding older TCRs
November 30, 2024 at 11:10 AM
Older TCRs had a lower binding avidity. The CD8 co-receptors enhanced binding avidity of age-specific private TCRs representing newborn, child, one adult and one older TCR, but had less impact on weak-binding older TCRs
To understand whether age-related functional changes of A2M1-specific CD8 T cells resulted from differential TCRαβ repertoires across age groups, we generated HEK293T-transient and SKW-3-stable cell lines encompassing full public or prominent age-specific TCRs
November 30, 2024 at 11:10 AM
To understand whether age-related functional changes of A2M1-specific CD8 T cells resulted from differential TCRαβ repertoires across age groups, we generated HEK293T-transient and SKW-3-stable cell lines encompassing full public or prominent age-specific TCRs
Public features in children and adults associated with robust A2M1-specific CD8 T cell proliferation. Ex vivo low-prevalent TCRs also proliferated upon in vitro stimulation, highlighting the importance of TCRαβ diversity. Furthermore, A2M1-specific CD8 T cell functionality peaks in children
November 30, 2024 at 11:10 AM
Public features in children and adults associated with robust A2M1-specific CD8 T cell proliferation. Ex vivo low-prevalent TCRs also proliferated upon in vitro stimulation, highlighting the importance of TCRαβ diversity. Furthermore, A2M1-specific CD8 T cell functionality peaks in children
Child and adult A2M1 TCRs, expressing TRBV19 public-associated CDR3α-‘GGGSQG’ and/or CDR3β-‘RS’ motifs, are easier to generate, explaining why they are shared between HLA-A*02:01-expressing individuals
November 30, 2024 at 11:10 AM
Child and adult A2M1 TCRs, expressing TRBV19 public-associated CDR3α-‘GGGSQG’ and/or CDR3β-‘RS’ motifs, are easier to generate, explaining why they are shared between HLA-A*02:01-expressing individuals
Public-associated CDR3α and β motifs, including dominant CDR3α ‘GGGSQG’ & CDR3β-‘RS’ motifs and less dominant public CDR3β “IG”, “YGY”, “IY” motifs became less frequent in older adults and were replaced with high-frequency private CDR3 motifs uniquely identified in a single individual
November 30, 2024 at 11:10 AM
Public-associated CDR3α and β motifs, including dominant CDR3α ‘GGGSQG’ & CDR3β-‘RS’ motifs and less dominant public CDR3β “IG”, “YGY”, “IY” motifs became less frequent in older adults and were replaced with high-frequency private CDR3 motifs uniquely identified in a single individual
Our data suggest that influenza virus exposures expand public TCRαβ clonotypes, dominated by TRAV27 and TRBV19 gene usage, in children and adults, which are replaced by private TCRαβ clonal expansions in older adults
November 30, 2024 at 11:10 AM
Our data suggest that influenza virus exposures expand public TCRαβ clonotypes, dominated by TRAV27 and TRBV19 gene usage, in children and adults, which are replaced by private TCRαβ clonal expansions in older adults
A2M1-specific TCRαβ repertoires are highly diverse in newborns, greatly cluster in children and adults, before diversifying in older adults. These changes are attributed to both TCR α-chains and β-chains
November 30, 2024 at 11:10 AM
A2M1-specific TCRαβ repertoires are highly diverse in newborns, greatly cluster in children and adults, before diversifying in older adults. These changes are attributed to both TCR α-chains and β-chains
A2M1-specific CD8 T cells have a nonlinear differentiation across human lifespan. Trajectory 1 newborns➡️children➡️adults toward effector cytotoxic T cells associated with optimal TCRs. Trajectory 2 dominated by older less-differentiated T cells of a distinct clonal lineage
November 30, 2024 at 11:10 AM
A2M1-specific CD8 T cells have a nonlinear differentiation across human lifespan. Trajectory 1 newborns➡️children➡️adults toward effector cytotoxic T cells associated with optimal TCRs. Trajectory 2 dominated by older less-differentiated T cells of a distinct clonal lineage
Gene expression profiles across human lifespan revealed naïve profiles in newborns, mixed naive/memory profiles in children, cytotoxic-effector-memory profiles in adults and inversion of naive profiles in older adults, without evidence for exhaustion/terminal differentiation
November 30, 2024 at 11:10 AM
Gene expression profiles across human lifespan revealed naïve profiles in newborns, mixed naive/memory profiles in children, cytotoxic-effector-memory profiles in adults and inversion of naive profiles in older adults, without evidence for exhaustion/terminal differentiation
The frequency of the A2M1-specific CD8 T cells peaked in adult and decreased in in older adults. Notably A2M1-specific CD8 T cells in older adults were not terminally differentiated and lacked expression of senescent markers like CD57, in contrast to total CD8 T cells
November 30, 2024 at 11:10 AM
The frequency of the A2M1-specific CD8 T cells peaked in adult and decreased in in older adults. Notably A2M1-specific CD8 T cells in older adults were not terminally differentiated and lacked expression of senescent markers like CD57, in contrast to total CD8 T cells
We defined influenza-specific CD8 T cell immunity across the human lifespan ex vivo in newborns, children, adults and older adults in CD8 T cells directed at the prominent/conserved HLA-A*02:01-restricted M1(58–66) peptide derived from influenza A viruses (A2M1)
November 30, 2024 at 11:10 AM
We defined influenza-specific CD8 T cell immunity across the human lifespan ex vivo in newborns, children, adults and older adults in CD8 T cells directed at the prominent/conserved HLA-A*02:01-restricted M1(58–66) peptide derived from influenza A viruses (A2M1)