Do epitopes derived form autoantigens display low affinity for MHC class I?

affinity of an epitope directiy, determine

MHC proteins or whether, like Ac1-9. they

the stability of the resulting compkxes’.

are inherently unstable.

tJs;ng this approach, Acl-9

forms

we have show”

exceptionally

we are grateful to

der Burg and col-

MC

unstabte

in fact that their

com-

tstinwtcd

only by empIo>l”g

cent wor!P,

chemical

means’“.

reviewing

:Se mechacisns of immuno-

shown

dominance

among epitopes with low at-

that

the

I-A=, so

half-iife

leagues for drawing our attention to their RL pubhshed since QU own article

that

onstzhk

plexes with the class II determinant

peptide

bio-

we have

9-20

complexes

can be

ser&tve

By contrast,

forms

km+

stab:?

fin@ for major h&torompatibtIity compkx

wrface

of viable ant@--pmenttng

wth

ex-

i-A” at the ceus-‘.

(MHC) determinants~. Their atudi+- .lem-

If, a, VJX der Burg and cokagws

so&+xt,

onstrate that, in spite of the tow affinia:; for

we assmxe

a” acco-

MHC class 1 displayed

by the immune

that stability

provides

rate indication

of immunogenic&y,

dominant epitopes of sotne tumoui antigens,

be anticipated

that 9-20 would

such peptides may dissociate surprisii~Iy

thv autoimmune

slowIy from the pepti.ie-binding groove, rc-

ity, however,

Surting in relzltively stable complexc~. fhus,

munodominance,

low affinity per br does not n~ws%rily

epitope

jeopardize presentation of wch epitopes to

Consequently,

the T-4

van der Burg and colIeagucs

repertoire

or even exclude

tape from assuming

a” epi-

it is Acl-9

physiologically

van der Burg and colleagus

consider

that

precisely with immunogenidty,

rontws

conclusions.

Irf the issues

a-vait clarification

dted

FmCeS.Sed epitopes

may support

the authors’

I-restricted

epitopes

claim

for

of self-pro-

teins, such as MART-I, it re”rd”s the

synthetic

peptides

studied

represent

the nahwaiiy

pmcessed

epitopcr

note

our ow” experiments

of caution

fkdings

when

studies

acetylated

of Acl-9,

such

epitopis

of

of myelin

basic

!MBp?, f&y endone the .orotei” physiological importance of measurements of stability;

indeed

have been based assays

that,

F E B ii

our own

on *e than

U

R Y

A

obiervaticn~

results

rather

resolution letter

most

the naturally

of autoantigens complexes

Tii dwences in T&e

the natur;tIIy

N-termmna1 epitope

by their

of whether stable

the

other with

Manmwe-bidfflg immunesystem.

cIa.sicaI autoantigens. Our

form

from

I

Immmml. T&y 17.80-85 4 Fat&&i, l?J.. WiId~wse, R. Athertcm. E., Web+, 5. zwd Wraith, D.C. (1993) Ink Immured. 5, 1151-X58 5 Mason. K and McGmneIl, H.M. (1994) Pm. h’nfl.Ami. Sci.IL S. A. 91,1246Z+l2466 6 hlasm, K, Daurey.D.W.and ?&C.mneII,H.NL 11995)/. fmm;inol.154,521&5227 7 F.G&iId, 9.. Pop+, H. alrd Wraith. D-C. w961 mr. If~Irr!enol.8, 1035-la43

Authorkc-

sound a

extrapokting

to the class II-restricted

MBP

to

uncertain

whether

Furthermote,

t-an

is more

nwy invite er-

Ultimately,

raised

26,1683-1689 3 Fas&iId, I’.].amt Wtith, DC (19%)

with

affinity,

in isolation

mutuaUv exclusive. While the experiments the dass

than

processing

why dominance and low affinity need not k

silent

agree

that the stabil-

complexes

stability

fomt? of antigen

1 vnn da Burg. S-H., Vine”?“, M.J.W., Brandt, Rh,_t? d al. WW J. Imnrimd.1563308-3314 2 van Ek+, A., van der Burg. S.H., ran der Mt, C.E. d 01.(19961 Eur. /. Immuriol.

im-

high-affinity

we folly

relevant

stability rather tbrm affinity correlates mo? explaining

that exhibits

immu”ologicaIIy

while

ity of peptide_MHC

the status of immono-

it might domina:e

to MBP. I” real-

the adjcent

remaining

dominance. On the basis of their findings, sug@

response

of cellular

mearrsucing

199

the

.

.-,

were