12. Antibodies are multi-domain proteins
secreted by B cells
VL CL VL
CL
VH VH
antigen
CH CH binding sites
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13. Antibody-encoding genes get randomly
rearranged in B cells to increase diversity
Germ Line DNA
Same
for all cells
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14. Antibody-encoding genes get randomly
rearranged in B cells to increase diversity
Variable Constant
Germ Line DNA
Same
for all cells
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15. Antibody-encoding genes get randomly
rearranged in B cells to increase diversity
Variable Constant
Germ Line DNA
Same
for all cells
Rearranged DNA
Unique to each
B cell (allele)
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16. Antibody-encoding genes get randomly
rearranged in B cells to increase diversity
Variable Constant
Germ Line DNA
Same
for all cells
Rearranged DNA
Unique to each
B cell (allele)
mRNA
2,644,240 potential
combinations
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17. B cells undergo fast natural
selection, which further
increases diversity
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18. B cells undergo fast natural
selection, which further
increases diversity
B cells
proliferate with
high mutation rate
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19. B cells undergo fast natural
selection, which further
increases diversity
B cells
proliferate with
high mutation rate
Follicular
Dendritic Cells
select for
binding affinity
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21. Effective antibodies differ on sequence
but share similar structures
VHeavy
VLight
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22. Effective antibodies differ on sequence
but share similar structures
VHeavy
VLight
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23. Effective antibodies differ on sequence
but share similar structures
VHeavy
VLight
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24. Effective antibodies differ on sequence
but share similar structures
VHeavy
VLight
Same germ
line allele
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25. Similar binding suggests convergent
evolution
Mature gp120
Germ Shared
Line Epitope
Paratope
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26. 110K reads of HC
from a single donor # Reads
Sequence
Identity
with
PG04 (%)
Germ line divergence (%)
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27. Sequencing reveals that divergent
antibodies are rare
110K reads of HC
from a single donor # Reads
Sequence
Identity
with
PG04 (%)
Germ line divergence (%)
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28. Sequencing reveals that neutralizing
antibodies are divergent
110K reads of HC
from a single donor
Sequence
Identity
with Effective
Non-effective
PG04 (%)
Germ line divergence (%)
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29. Sequencing reveals maturation lineages
110K reads of HC
from a single donor
Sequence Same CDR
H3 Family
Identity
with
PG04 (%)
Germ line divergence (%)
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30. Sequencing reveals maturation lineages
110K reads of HC
from a single donor
Sequence Same CDR
H3 Family
Identity
with
PG04 (%)
Good
Neutralizer
Germ line divergence (%)
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31. Cross-donor phylogenetic
analysis can identify
neutralizing
antibodies
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32. Cross-donor phylogenetic
analysis can identify
neutralizing
antibodies
High performing
antibodies from
other patients
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33. Cross-donor phylogenetic
analysis can identify
neutralizing
antibodies
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34. gp140
Cross-donor phylogenetic
analysis can identify
neutralizing
23 mutations
antibodies
germ
line 41 mutations
56 mutations
93 mutations
VRC03
High
Performing
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35. High performing
intermediates
could form the
basis of an
effective
HIV vaccine
miércoles 4 de abril de 12
